GİRİŞ ve AMAÇ: Ganoderma adsperum, Inonotus hispidus, Russula chloroides ve Sarcodon imbricatus mantar türlerinin etanolik özütleri, polifenolik içerikleri ve biyolojik aktiviteleri açısından araştırılmıştır.
YÖNTEM ve GEREÇLER: Ekstrelerin radikal süpürücü etkileri DPPH (2,2-Difenil-1-(2,4,6-trinitrofenil) yöntemi kullanılarak ve polifenolik içerikleri HPLC analizleri ile belirlendi. Ayrıca, mantar ekstrelerinin GST (glutatiyon-S-transferaz) enzim aktivatör etkisi incelenmiştir. Bunlara ek olarak, mantar ekstrelerinin antimikrobiyal aktivitesi, disk difüzyon yöntemi ile değerlendirildi.
BULGULAR: I. hispidus’un etanol ekstresi sırasıyla 227.23 ± 4.96 mg GAE/g ve 42.14 ± 0.20 QE/g değerleri ile en yüksek toplam fenol ve toplam flavonoid içeriğini göstermiştir. DPPH radikalini en yüksek temizleme aktivitesi de I. hispidus'un etanol ekstresinde, 10.687 ± 1.643 µg/mL IC50 değeri ile gözlenmiştir. HPLC analizi, R. chloroides’in ferulik asit, gallik asit ve mirisetin bileşiklerinden oluştuğunu göstermiştir. En yüksek GST enzim aktivatör etki I. hispidus ve S. imbricatus’un etanol ekstrelerinde belirlenmiştir. Mantar ekstrelerinin hiçbiri kullanılan bakteri suşları üzerinde belirgin bir inhibisyon göstermemiştir.
TARTIŞMA ve SONUÇ: Bu sonuçlar, ileri araştırmalar gerektirip I. hispidus’un yeni bir potansiyel doğal ilaç kaynağı olabileceğini ve bu potansiyelin polifenolik içeriği ile ilişkili olabileceğini göstermektedir.

INTRODUCTION: Ethanolic extracts of Ganoderma adsperum, Inonotus hispidus, Russula chloroides and Sarcodon imbricatus mushroom species were investigated for their polyphenolic contents and biological activities.
METHODS: The radical scavenging activity of the extracts were evaluated by using DPPH 2,2-Diphenyl-1-(2,4,6-trinitrophenyl) method and their polyphenolic compounds were determined by HPLC analysis. Furthermore, the activity effects of mushroom extracts on the GST (glutathione-S-transferase) enzyme were also examined. Additionally, antimicrobial activity of mushroom extracts were evaluated with disc diffusion method.
RESULTS: Ethanolic extract of I. hispidus demonstrated the highest total phenolic content and total flavonoid contents with 227.23 ± 4.96 mg gallic acid equivalent/g and 42.14 ± 0.20 quercetin equivalent/g values, respectively. The highest DPPH radical scavenging activity was also observed for ethanolic extracts of I. hispidus with 10.687 ± 1.643 µg/mL IC50 value. HPLC analysis demonstrated that R. Chloroides was comprised of ferulic acid, gallic acid and myricetin compounds. The highest GST enzyme activity effect was detected by the ethanol extracts of I. hispidus and S. imbricatus. None of the mushroom extracts demonstrated significant inhibition on the bacteria strains used.
DISCUSSION AND CONCLUSION: These results indicate that I. hispidus may be proposed as a new potential source of natural medicine and its potential may be related to its polyphenolic content, which needs further investigation.

Abstract | Full Text PDF

INTRODUCTION: Objectives: Mycobacterium tuberculosis is a causative organism of tuberculosis, which is most lethal disease after cancer in a current decade. The development of multidrug and broadly drug-resistant strains making the tuberculosis problem more and more critical. In last 40 years, only one molecule is added to the treatment regimen. Generally, drug design and development programs are targeted proteins whose function is known to be essential to the bacterial cell. M. tuberculosis possesses specialized protein export systems like SecA2 export pathway and ESX pathways.
Material and methods: In the present communication, rational development of anti-mycobacterial agent's targeting protein export system has been carried out by integrating the pocket modeling and virtual analysis.
Results: The identified potential 23 lead compounds were synthesized, characterized by physicochemical and spectroscopic methods like IR, NMR spectroscopy and further screened for anti-mycobacterial activity using isoniazid as standard. All the designed compounds have shown profound anti-mycobacterial activity.
Conclusion: In this present communication, we found that M26, U8, and R26 molecules had significant desirable biological activity and specific interactions with Sec of mycobacteria. Further optimization of these leads is necessary for the development of potential anti-mycobacterial drug candidate less side effects.
METHODS: . Experimental
2.1 Selection of Target:
Mycobacterium tuberculosis is three specialized protein export systems like SEC, TAT, and ESX. Secondary translocase pathway (SEC) is major protein export systems of MTB, which export bulk of virulent protein, which accounts for the spread of disease. SEC systems are not having any homologs in mammalian systems, so inhibition of this SEC will not lead to any toxicity to the human being. Thus due to the critical role of the SEC in the growth and virulence of the MTB, SEC has been selected as preferred biomolecular target than TAT and ESX
2.2 Pocket modeling of selected protein export systems;
Pocket modeling of the selected SEC of MTB was carried out using crystal structure of SEC downloaded from the free protein database www.rcsb.org. Downloaded crystal structure of SEC (PDBID 1QNX) was first refined using biopredicta molecule, via removal of water molecules and retaining native hydrogen atoms in the protein structure. Pocket modeling of SEC A is carried out using proviz module of Vlife MDS 4.4. Proviz is integrated property visualization module using which electrostatic and hydrophobic mapping of biomolecules can be carried out.
2.3 Design of molecules:
Pocket modeling of the SEC revealed the binding pocket of SEC is U shaped and highly hydrophobic, keeping in mind complementary structures on thiazole template were designed with structural modification on the aromatic moiety has been carried out. A number of the aromatic benzaldehyde are utilized to generate number of thiazole derivatives. Total 75X75 benzaldehyde combinations are utilized to generate total 5625 different structures (indicated as R) as shown in table 1. These 5625 different thiazole derivatives were designed and drawn in 2D geometry using builder module of the Vlife MDS 4.4. 2D structures are converted into the 3D geometry and their coordinates were optimized via energy minimization process via application of Merck molecular force field (MMFF)
2.4. Docking analysis of synthesized ligands
Molecular docking was performed to identify potent derivatives with the maximum binding affinity for SEC of MTB amongst the designed set of molecules. Docking analysis was performed in the biopredicta module of the Vlife MDS 4.4 using grip based docking analysis in which protein structure was kept rigid and molecules are kept the flexible conformation so that number of conformation can be achieved. Best 100 confirmation of the each designed molecules were generated. Potent molecules were scrutinized based on binding energy and interaction profile. The proposed synthetic scheme of designed derivatives is shown in Fig. 1.
2.5. Screening based on the drug-like properties and percentage absorption.
Designed set of molecules were analyzed for Lipinski parameters like molecular weight, H-bond acceptor, H-bond donor, Rotatable bond, XlogP etc. The physicochemical descriptors calculated with the help of QSAR module of Vlife MDS 4.4. Total polar surface area (TPSA) calculated from the web server www. molinspiration.com/cgi-bin/properties by drawing the molecules in drawing area then calculates the TPSA. Percentage absorption was calculated by using the formula, % Absorption = 109 - (0.345 x TPSA).21


Table No. 1: Designed set of molecules (Total 75X75 benzaldehyde combinations are utilized to generate total 5625 different structures indicated as R)
Sr. no. R Sr. no. R Sr. no. R Sr. no. R
1. C6H5 2. 4- (CH3)2 N-C6H5 3. 4CH3CONH- C6H5 4. 2-OCHC6H5
5. 3- OCHC6H5 6. 4- OCHC6H5 7. 3- OCH,4-OCH3- C6H4 8. 5-Br-2-OH- C6H4
9. 2-Br- C6H5 10. 3-Br- C6H5 11. 4-Br- C6H5 12. 2-Cl-6-F- C6H4
13. 4-Cl-3-NO2 14. 2-Cl- C6H5 15. 3-Cl- C6H5 16. 4-Cl- C6H5
17. 2-(4-Cl-SC6H5) 18. 3-CN- C6H5 19. 4-CN- C6H5 20. 2,3-Cl- C6H4
21. 2,4-Cl-C6H4 22. 2,6-Cl- C6H4 23. 3,5-Cl- C6H4 24. 4-(C2H5)2N- C6H5
25. 2,6-F-C6H4 26. 3,4-F- C6H4 27. 2,3-OH- C6H4 28. 2,4-OH- C6H4
29. 2,5-OH-C6H4 30. 3,4-OH-C6H4 31. 2,3-OCH3- C6H4 32. 2,4-OCH3- C6H4
33. 2,5-OCH3 34. 3,4- OCH3-C6H4 35. 3,5- OCH3- C6H4 36. 3,5- OCH3,4-OH- C6H4
37. 2,4-CH3-C6H4 38. 3,5-CH3-C6H4 39. 3-OC2H5-4-OH- C6H4 40. 2-F-C6H5
41. 3-F-C6H5 42. 4-F-C6H5 43. 2-OH- C6H5 44. 3-OH-C6H5
45. 4-OH-C6H5 46. 2-OH,3-OCH3- C6H4 47. 2-OH,4-OCH3- C6H4 48. 2-OH,5-OCH3-C6H4
49. 3-OH,4-OCH3 C6H4 50. 4-OH,3-OCH3-5NO2 51. 2-OH-5NO2 52. 4-CH(CH3)2-C6H5
53. 2-OCH3-C6H5 54. 3-OCH3-C6H5 55. 4-OCH3-C6H5 56. 4-CH3-C6H5
57. 2-CH3-C6H5 58. 3-CH3-C6H5 59. 4-SCH3-C6H5 60. 2-NO2-C6H5
61. 3-NO2-C6H5 62. 4-NO2-C6H5 63. 3-OC6H5 64. 4-CH(CH3)3- C6H5
65. 2,3,5-Cl C6H3 66. 3,4,5-F-C6H3 67. 4-CF3OCH3-C6H4 68. 4-CF3-C6H5
69. 2,3,4-OCH3-C6H3 70. 3,4,5-OCH3-C6H3 71. 2,4,6-OCH3-C6H3 72. 3-NO2-C6H5
73. C5H4O2 74. C9H10O3 75. C5H4OS


2.6 Synthesis of selected ligands 22
2.6.1 Synthesis of optimized thiazole derivatives
Step 1
Synthesis of 2-amino-5-aryl-5H thiazolo[ 4,3-b]-l,3,4-thiadiazole (1)
In 25ml RBF Aldehyde (0.02M) and thioglycolic acid (0.02M), thiosemicarbazide (0.022M) and 10ml of concentrated H2SO4 were taken. The reaction mixture was mixed and left overnight and the resulting suspension was neutralized with 40% NaOH solution till product gets precipitated out and this resulting compound 1was recrystallized from aqueous dioxane solution.
Synthesis of 1-phenyl-N-{5-phenyl-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl}methanimine derivatives(2):
A solution of compound 1 (0.01M) in ethanol (50ml) was taken in RBF and stirred vigorously for 15 minutes to this resulting solution concentrated H2SO4 (2ml) and aldehyde (0.01M) was added. The reaction mixture was irradiated in the synthetic microwave (Cata 4R) for 10min. The separated solid was filtered and recrystallized from ethanol.
Synthesis of 2-phenyl-3-{5-phenyl-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl}-1,3- thiazolidin-4-one derivatives (3):
In 25ml RBF compound, 2 (0.01M) and thioglycolic acid (0.01M) were taken and DMF 30ml was added and stirred. Resulting reaction mixture was irradiated in the microwave for 10 min at 750 watts. The reaction mixture was cooled to room temperature and resulting solid was separated and recrystallized from benzene to get compound 1 to 23. Table 2 shown list of substituents in the synthesized set of molecules.
Table No. 2: List of Substituents in Synthesized set of molecules
Sr. No. R1 R2 Code
1. 4-Br-C6H4 -C6H4 B3
2. -C6H4 4-Cl-C6H4 C13
3. -C6H4 2-Cl-C6H4 C1
4. 3,4-(OCH3)-C6H4 2-Cl-C6H4 F1
5. 2-(OH)-C6H4 3-Cl-C6H4 O17
6. -C4H3O 3-OCH3-4-OH-C6H3 Q21
7. 4-N(CH3)2-C6H4 4-Cl-C6H4 L13
8. 2-(OH)-C6H4 4-Cl-C6H4 O13
9. -C4H3O 2-(OH)-C6H4 Q24
10. 4-Cl-C6H4 4-(OH)-C6H4 M9
11. 4-F-C6H4 -C4H3O H25
12. 3-Cl-C6H4 S-C4H3 R26
13. 3-(OCH3)-4-(OH)-C6H3 -C6H4 V3
14. 3,5-(OCH3)2-4-(OH)C6H2 -C6H4 U8
15. 3-Cl-C6H4 3-NO2-C6H4 A11
16. 2-Cl-C6H4 4-NO2-C6H4 A10
17. -C4H3O 3-OCH3-C6H4 Q22
18. -C4H3O -C7H5O2 Q30
19. 3-Cl-C6H4 S-C4H3 R25
20. 4-Cl-C6H4 S-C4H3 M26
21. 3-Cl-C6H4 3,4-(OCH3)-C6H4 R6
22. 3-(OCH3)-C6H4 4-Cl-C6H4 W13
23. 3-(OCH3)-C6H4 4-F-C6H4 W8

B3: 3-[5-(4-bromophenyl)-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl]-2-phenyl-1,3 thiazolidin-4-one
Color: Brown, Yield: 82%, m. p.: 192-194°C, MASS: [M+1]+ 474.94, IR: 1752 cm-1 (C=O Str.), 1452 cm-1 (C=C), 2742.84 cm-1 (Ar. CH), 1580 cm-1 (-N=CH) NMR: 1H NMR (DMSO-d6, 300 MHz,): δ = 6.95-7.35 (m, 9H, aromatic H), 4.95-5.90 (s, 2H, methine), 3.35 (s, 2H, methylene), 4.85 (s, 1H, ethylene)
C13: 2-(4-chlorophenyl)-3-{5-phenyl-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl}-1,3-thiazolidin-4-one
Color: Yellow, Yield: 80%, m. p.: 178-180°C, MASS: [M+1]+ 430.99, IR: 1690 cm-1 (C=O Str.), 1435 cm-1 (C=C), 2842 cm-1 (Ar. CH), 1470 cm-1 (-N=CH), NMR: 1H NMR (DMSO-d6, 300 MHz,): δ = 6.90-7.25 (m, 9H, aromatic), 4.95-5.90 (s, 2H, methine), 3.38 (s, 2H, methylene), 4.95 (s, 1H, ethylene)
C1: 2-(2-chlorophenyl)-3-{5-phenyl-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl}-1,3-thiazolidin-4-one
Color: Brown, Yield: 75%, m. p.: 186-188°C, MASS: [M+1]+ 430.99, IR: 1625 cm-1 (C=O Str.), 1400 cm-1 (C=C), 2830 cm-1 (Ar. CH), 1476 cm-1 (-N=CH) NMR: 1H NMR (DMSO-d6, 300 MHz,): δ = 6.95-7.20 (m, 9H, aromatic), 4.90-5.92 (s, 2H, methine), 3.30 (s, 2H, methylene), 4.90 (s, 1H, ethylene)
F1: 2-(2-chlorophenyl)-3-[5-(3,4-dimethoxyphenyl)-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl]-1,3-thiazolidin-4-one
Color: Lemon, Yield: 89%, m. p.: 162-164°C, MASS: [M+1]+ 492.02, IR: 1640 cm-1 (C=O Str.), 1490 cm-1 (C=C), 2790 cm-1 (Ar. CH), 1520 cm-1 (-N=CH) NMR: 1H NMR (DMSO-d6, 300 MHz,): δ = 6.52-7.15 (m, 7H, aromatic), 4.95-5.90 (s, 2H, methine), 3.33 (s, 2H, methylene), 4.85 (s, 1H, ethylene), 3.75 (d, 6H, methyl)
O17: 2-(3-chlorophenyl)-3-[5-(2-hydroxyphenyl)-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl]-1,3-thiazolidin-4-one
Color: Yellow, Yield: 80%, m. p.: 228-230°C, MASS: [M+1]+ 447.97, IR: 1680 cm-1 (C=O Str.), 1500cm-1 (C=C), 2810 cm-1 (Ar. CH), 1580 cm-1 (-N=CH) NMR: 1H NMR (DMSO-d6, 300 MHz,): δ = 6.62-7.20 (m, 8H, aromatic), 4.95 (s, 1H, methine), 5.92 (s, 1H, methine), 3.38 (s, 1H, methylene), 4.75 (s, 1H, ethylene), 6.05 (s, 1H, aromatic C-OH)
Q21: 2-(3-ethoxy-4-hydroxyphenyl)-3-[5-(furan-2-yl)-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl]-1,3-thiazolidin-4-one
Color: Black, Yield: 78%, m. p.: 192-194°C, MASS: [M+1]+ 447.54, IR: 1750 cm-1 (C=O Str.), 1540 cm-1 (C=C), 2840 cm-1 (Ar. CH), 1600 cm-1 (-N=CH) NMR: 1H NMR (DMSO-d6, 300 MHz,): δ = 6.05-7.30 (m, 6H, aromatic benzene and furan), 4.75 (s, 1H, ethylene), 5.15-5.92 (s, 2H, methine), 3.30 (s, 2H, methylene), 3.95 (s, 2H, methylene), 1.58 (s, 3H, methyl), 5.02 (s, 1H aromatic C-OH)
L13: 2-(4-chlorophenyl)-3-{5-[4-(dimethylamino)phenyl]-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl}-1,3-thiazolidin-4-one
Color: Brown, Yield: 67%, m. p.: 156-158°C, MASS: [M+1]+ 475.04, IR: 1652 cm-1 (C=O Str.), 1538 cm-1 (C=C), 2800 cm-1 (Ar. CH), 1530 cm-1 (-N=CH) NMR: 1H NMR (DMSO-d6, 300 MHz,): δ = 6.45-7.20 (m, 8H, aromatic benzene), 4.80 (s, 1H, ethylene), 4.95-5.80 (s, 2H, methine), 3.30 (s, 2H, methylene), 2.95 (s, 6H, methyl N-CH3)
O13: 2-(4-chlorophenyl)-3-[5-(2-hydroxyphenyl)-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl]-1,3-thiazolidin-4-one
Color: Brown, Yield: 67%, m. p.: 236-238°C, MASS: [M+1]+ 447.97, IR: 1760 cm-1 (C=O Str.), 1540 cm-1 (C=C), 2830cm-1 (Ar. CH), 1680 cm-1 (-N=CH) NMR: 1H NMR (DMSO-d6, 300 MHz,): δ = 6.65-7.25 (m, 8H, aromatic benzene), 4.85 (s, 1H, ethylene), 4.05-4.70 (s, 2H, methine), 3.28 (s, 2H, methylene), 5.25 (s, 1H, aromatic C-OH)
Q24: 3-[5-(furan-2-yl)-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl]-2-(2-hydroxyphenyl)-1,3-thiazolidin-4-one
Color: Black, Yield: 75%, m. p.: 216-218°C, MASS: [M+1]+ 403.49, IR: 1740 cm-1 (C=O Str.), 1623 cm-1 (C=C), 2810 cm-1 (Ar. CH), 1680 cm-1 (-N=CH), NMR: 1H NMR (DMSO-d6, 300 MHz,): δ = 6.60-7.30 (m, 7H, aromatic benzene and furan), 4.80 (s, 1H, ethylene), 5.20-5.80 (s, 2H, methine), 3.30 (s, 2H, methylene), 5.25 (s, 1H, aromatic C-OH)
M9: 3-[5-(4-chlorophenyl)-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl]-2-(4-hydroxyphenyl)-1,3-thiazolidin-4-one
Color: Brown, Yield: 88%, m. p.: 138-140°C, MASS: [M+1]+ 447.97, IR: 1700 cm-1 (C=O Str.), 1640 cm-1 (C=C), 2790 cm-1 (Ar. CH), 1650 cm-1 (-N=CH), NMR: 1H NMR (DMSO-d6, 300 MHz,): δ = 6.55-7.25 (m, 8H, aromatic benzene), 4.85 (s, 1H, ethylene), 5.10-5.85 (s, 2H, methine), 3.38 (s, 2H, methylene), 6.05 (s, 1H, aromatic C-OH)
H25: 3-[5-(4-fluorophenyl)-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl]-2-(furan-2-yl)-1,3-thiazolidin-4-one
Color: Yellow, Yield: 70 %, m. p.: 122-124°C, MASS: [M+1]+ 405.48, IR: 1688 cm-1 (C=O Str.), 1589 cm-1 (C=C), 2690 cm-1 (Ar. CH), 1580 cm-1 (-N=CH) NMR: 1H NMR (DMSO-d6, 300 MHz,): δ = 6.30-7.05 (m, 7H, aromatic benzene and furan), 4.82 (s, 1H, ethylene), 5.10-5.85 (s, 2H, methine), 3.35 (s, 2H, methylene)
R26: 3-[5-(3-chlorophenyl)-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl]-2-(thiophen-2-yl)-1,3-thiazolidin-4-one
Color: Yellow, Yield: 72%, m. p.: 206-208°C, MASS: [M+1]+ 437.99, IR: 1750 cm-1 (C=O Str.), 1670 cm-1 (C=C), 2560 cm-1 (Ar. CH), 1540 cm-1 (-N=CH) NMR: 1H NMR (DMSO-d6, 300 MHz,): δ = 6.60-7.10 (m, 7H, aromatic benzene and thiophene), 4.85 (s, 1H, ethylene), 4.95-5.90 (s, 2H, methine), 3.30 (s, 2H, methylene)
V3: 3-[5-(3-ethoxy-4-hydroxyphenyl)-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl]-2-phenyl-1,3-thiazolidin-4-one
Color: Brown, Yield: 83%, m. p.: 180-182°C, MASS: [M+1]+ 457.58, IR: 1620 cm-1 (C=O Str.), 1560 cm-1 (C=C), 2860 cm-1 (Ar. CH), 1490 cm-1 (-N=CH) NMR: 1H NMR (DMSO-d6, 300 MHz,): δ = 6.45-7.14 (m, 8H, aromatic benzene), 4.80 (s, 1H, ethylene), 4.90-5.85 (s, 2H, methine), 3.35 (s, 2H, methylene), 5.95 (s, 1H, aromatic C-OH), 3.98 (s, 2H, methylene), 1.75 (s, 3H, methyl)
U8: 3-[5-(4-hydroxy-3,5-dimethoxyphenyl)-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl]-2-phenyl-1,3-thiazolidin-4-one
Color: Yellow, Yield: 80%, m. p.: 230-232°C, MASS: [M+1]+ 473.58, IR: 1688 cm-1 (C=O Str.), 1562 cm-1 (C=C), 2883 cm-1 (Ar. CH), 1489 cm-1 (-N=CH) NMR: 1H NMR (DMSO-d6, 300 MHz,): δ = 5.95-7.10 (m, 7H, aromatic benzene), 4.85 (s, 1H, ethylene), 4.92-5.95 (s, 2H, methine), 3.28 (s, 2H, methylene), 5.98 (s, 1H, aromatic C-OH), 3.85 (s, 6H, methoxy)
A11: 3-[5-(3-chlorophenyl)-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl]-2-(3-nitrophenyl)-1,3-thiazolidin-4-one
Color: Brown, Yield: 69 %, m. p.: 146-148°C, MASS: [M+1]+ 476.97, IR: 1679cm-1 (C=O Str.), 1575 cm-1 (C=C), 2896 cm-1 (Ar. CH), 1523 cm-1 (-N=CH). NMR: 1H NMR (DMSO-d6, 300 MHz,): δ = 6.90-7.95 (m, 8H, aromatic benzene), 4.75 (s, 1H, ethylene), 4.90-5.92 (s, 2H, methine), 3.33 (s, 2H, methylene)
A10: 3-[5-(2-chlorophenyl)-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl]-2-(4-nitrophenyl)-1,3-thiazolidin-4-one
Color: Brown, Yield: 70%, m. p.: 174-176°C, MASS: [M+1]+ 476.97, IR: 1590 cm-1 (C=O Str.), 1456 cm-1 (C=C), 2675 cm-1 (Ar. CH), 1563 cm-1 (-N=CH). NMR: 1H NMR (DMSO-d6, 300 MHz,): δ = 7.04-8.05 (m, 8H, aromatic benzene), 4.85 (s, 1H, ethylene), 4.95-5.90 (s, 2H, methine), 3.28 (s, 2H, methylene)
Q22: 3-[5-(furan-2-yl)-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl]-2-(3-methoxyphenyl)-1,3-thiazolidin-4-one
Color: Black, Yield: 78 %, m. p.: 176-178°C, MASS: [M+1]+ 417.52, IR: 1639 cm-1 (C=O Str.), 1420 cm-1 (C=C), 2640 cm-1 (Ar. CH), 1570 cm-1 (-N=CH). NMR: 1H NMR (DMSO-d6, 300 MHz,): δ = 6.50-7.30 (m, 7H, aromatic benzene and furan), 4.80 (s, 1H, ethylene), 5.10-5.95 (s, 2H, methine), 3.30 (s, 2H, methylene), 3.75 (s, 3H, methoxy)
Q30: 2-(2H-1,3-benzodioxol-5-yl)-3-[5-(furan-2-yl)-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl]-1,3-thiazolidin-4-one
Color: Black, Yield: 70%, m. p.: 240-242°C, MASS: [M+1]+ 431.50, IR: 1782 cm-1 (C=O Str.), 1560 cm-1 (C=C), 2785 cm-1 (Ar. CH), 1630 cm-1 (-N=CH). NMR: 1H NMR (DMSO-d6, 300 MHz,): δ = 6.45-7.25 (m, 6H, aromatic benzene and furan), 4.82 (s, 1H, ethylene), 5.15-5.85 (s, 2H, methine), 3.28 (s, 2H, methylene), 5.95 (s, 2H, 1,3-dioxole)
R25: 3-[5-(3-chlorophenyl)-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl]-2-(thiophen-2-yl)-1,3-thiazolidin-4-one
Color: Yellow, Yield: 82%, m. p.: 234-236°C, MASS: [M+1]+ 437.99 IR: 1700 cm-1 (C=O Str.), 1590 cm-1 (C=C), 2693 cm-1 (Ar. CH), 1578 cm-1 (-N=CH). NMR: 1H NMR (DMSO-d6, 300 MHz,): δ = 6.65-7.05 (m, 7H, aromatic benzene and thiophene), 4.85 (s, 1H, ethylene), 4.95-5.95 (s, 2H, methine), 3.32 (s, 2H, methylene)
M26: 3-[5-(4-chlorophenyl)-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl]-2-(thiophen-2-yl)-1,3-thiazolidin-4-one
Color: Brown, Yield: 70%, m. p.: 210-212°C, MASS: [M+1]+ 437.99, IR: 1665 cm-1 (C=O Str.), 1545 cm-1 (C=C), 2530 cm-1 (Ar. CH), 1540 cm-1 (-N=CH). NMR: 1H NMR (DMSO-d6, 300 MHz,): δ = 6.60-7.25 (m, 7H, aromatic benzene and thiophene), 4.82 (s, 1H, ethylene), 4.90-5.92 (s, 2H, methine), 3.35 (s, 2H, methylene)
R6: 3-[5-(3-chlorophenyl)-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl]-2-(3,4 dimethoxyphenyl)-1,3-thiazolidin-4-one
Color: Brown, Yield: 85%, m. p.: 226-228°C, MASS: [M+1]+ 492.02, IR: 1675 cm-1 (C=O Str.), 1553 cm-1 (C=C), 2542 cm-1 (Ar. CH), 1580 cm-1 (-N=CH). NMR: 1H NMR (DMSO-d6, 300 MHz,): δ= 6.50-7.15 (m, 7H, aromatic benzene), 4.82 (s, 1H, ethylene), 4.92-5.85 (s, 2H, methine), 3.33 (s, 2H, methylene), 3.75 (s, 6H, methoxy)
W13: 2-(4-chlorophenyl)-3-[5-(3-methoxyphenyl)-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl]-1,3-thiazolidin-4-one
Color: White, Yield: 78%, m. p.: 170-172°C, MASS: [M+1]+ 462.00, IR: 1600 cm-1 (C=O Str.), 1532cm-1 (C=C), 2520 cm-1 (Ar. CH), 1560 cm-1 (-N=CH).NMR: 1H NMR (DMSO-d6, 300 MHz,): δ= 6.55-7.20 (m, 8H, aromatic benzene), 4.85 (s, 1H, ethylene), 4.92-5.88 (s, 2H, methine), 3.30 (s, 2H, methylene), 3.78 (s, 3H, methoxy)
W8: 2-(4-fluorophenyl)-3-[5-(3-methoxyphenyl)-5H-[1,3]thiazolo[4,3-b][1,3,4]thiadiazol-2-yl]-1,3-thiazolidin-4-one
Color: Brown, Yield: 80%, m. p.: 160-162°C, MASS: [M+1]+ 445.55 IR: 1750 cm-1 (C=O Str.), 1682cm-1 (C=C), 2540 cm-1 (Ar. CH), 1670 cm-1 (-N=CH). NMR: 1H NMR (DMSO-d6, 300 MHz,): δ = 6.65-7.05 (m, 8H, aromatic benzene), 4.80 (s, 1H, ethylene), 4.85-5.90 (s, 2H, methine), 3.34 (s, 2H, methylene), 3.65 (s, 3H, methoxy)
2.8 Antitubercular Activity:
The synthesized molecules were evaluated for antimycobacterial activity by culturing Mycobacterium smegmatis (NCIM 5138) on Middlebrook 7H9 broth (Difco) containing 0.5% albumin, 0.085% NaCl, 0.2% glucose, 0.05% Tween 80, and 0.5% glycerol at 37°C for 48 hr to mid-log phase (optical density at 600 nm [OD600]= 0.5) MICs of antibiotics against Mycobacterium smegmatis were determined in Middlebrook 7H9 broth by the standard microdilution method. All synthesized derivatives were dissolved in dimethyl sulfoxide and utilized for antimycobacterial assay in concentration range of (3.25-1000µgm/ml)

RESULTS: RESULTS AND DISCUSSION
Pocket modeling of SEC of Mycobacterium tuberculosis:
The binding pocket analysis was performed on the X-ray structure of the SEC from MTB downloaded from free protein database www.rcsb.org. Proviz module of Vlife MDS 4.4 was utilized to perform the pocket analysis. Electrostatic and hydrophobic map of the binding pocket of SEC was generated to identify the relative orientation of critical amino acids. Pocket modeling of SEC revealed the binding pocket of SEC is highly hydrophobic and ASP224, HIS534, and LYS115 are the three important amino acids required for the ATP binding. Fig. 2 showing the hydrophobic map of the active site of SEC of Mycobacterium tuberculosis. SEC runs protein export, which is driven by ATP as the energy source, inhibition of this ATP binding, or blocking three amino acids will inhibit the SEC and ultimately protein export. Binding pocket of SEC was found to be highly hydrophobic and U shaped. Molecules were designed with an intent so that they will retain necessary hydrophobicity and relative conformation with respect to the SEC of MTB. Molecules are developed keeping thiazole as the template, thiazole derivatives due presence of two heteroatoms which will act as an anchor and two aromatic rings will act as wings to the nucleus and capable of achieving the bioactive U or V-shaped conformation which is complementary to the binding site of SEC. Aromatic benzaldehydes are utilized to manipulate the required hydrophobic characters and from aromatic interaction with Histidine 534.
Screening based on the drug-like properties:
Pharmacokinetic properties of the molecules are an important factor in the conversion of any New Chemical Entity to the drug. Pre-assessment of this drug like properties is played a vital role in the selection of potential drug-like candidates from designed data set of the molecules. All the molecules in the designed set of thiazole derivatives were assessed for the Lipinski parameters like molecular weight, H-bond acceptor, H-bond donor, Rotatable bond logp and Predicted oral absorption. 23 derivatives were found to have desired pharmacokinetic properties and predicted oral absorption <70%. The selected 23 derivatives with the drug-like properties were given in the following table 3.
Table No. 3: Table showing the molecules having the desired drug-like properties
Sr. No. Compound Code Mole. Wt. H-Acce H-Donor Count RBC logP TPSA
(Å) Pre. % Oral Abs.
1 A10 476.988 4 0 4 4.738 44.81 93.54
2 A11 476.988 4 0 4 4.738 81.4 80.91
3 B3 476.442 1 0 3 4.939 35.57 96.72
4 C1 431.99 1 0 3 4.83 35.57 96.72
5 C13 431.99 1 0 3 4.83 35.57 96.72
6 F1 492.043 3 0 7 4.847 54.04 90.35
7 H25 405.498 2 0 3 3.908 46.57 85.26
8 L13 475.059 2 0 6 4.896 41.37 94.72
9 M9 447.99 2 1 4 4.535 58.63 88.77
10 M26 438.019 1 0 3 4.891 35.57 96.72
11 O13 447.99 2 1 4 4.535 58.63 88.77
12 O17 447.99 2 1 4 4.535 58.63 88.77
13 Q21 447.56 3 1 7 3.873 81 81.05
14 Q22 417.534 2 0 5 3.778 57.95 89.00
15 Q24 433.533 3 1 6 3.483 81 81.05
16 Q30 431.517 1 0 3 3.498 67.18 85.82
17 R6 492.043 3 0 7 4.847 54.04 90.35
18 R25 421.952 1 0 3 4.423 48.71 92.19505
19 R26 438.019 1 0 3 4.891 35.57 96.72
20 U8 491.588 5 1 8 4.038 77.1 82.40
21 V3 457.598 3 1 7 4.28 67.86 85.58
22 W8 445.562 3 0 5 4.324 44.81 93.54
23 W13 462.017 2 0 5 4.838 44.81 93.54

Molecular Docking:
Molecular docking was utilized to predict the potential active inhibitors from the designed set of ligands. Grip-based docking analysis was performed with maintaining the SEC in rigid conformation while ligands in flexible conformation. All the design set of molecules were found to be binding to the same binding site to that of ATP in SEC. The designed set of molecules were found to be interacting with HIS 534 and ASP224 via formation with hydrogen bond interaction and pi-stacking interaction. Binding interactions of selected 23 molecules were summarized in the following table no. 4, whereas Fig. 3, 4, 5 and 6 showing most active conformation of molecule M26, U8, R26 and A10 (Ball and Stick) with PDB ID 4UAQ respectively.
Table No. 4: Binding interactions and energy of docked molecules
Sr. No. Compound Code Binding Energy H-bond Pi-Stacking
1. A10 -33.43 HIS534 HIS534
2. A11 -0.12 HIS534 HIS534
3. B3 -35.40 HIS534 HIS534
4. C1 -7.41 ASP224 HIS534
5. C13 -2.31 HIS534
HIS534 HIS534
6. F1 -33.32 HIS534 HIS534
7. L13 -8.74 HIS534 HIS534
8. M9 -37.54 ASP219 HIS534
9. M26 -38.54 ASP224 HIS534
10. O13 -11.91 GLN498 HIS534
11. O17 -9.81 HIS534 HIS534
12. Q21 23.92 ASP219 HIS534
13. Q22 -11.97 HIS534 HIS534
14. Q24 -11.03 HIS534 HIS534
15. Q30 -3.89 HIS534 HIS534
16. R25 -2.51 HIS534 HIS534
17. R26 -4.66 ASP224 HIS534
18. R6 -11.74 HIS534 HIS534
19. U8 -0.21 HIS534 HIS534
20. V3 -36.40 HIS534 HIS534
21. H25 -8.37 HIS534 HIS534
22. W8 -33.40 ASP224 HIS534
23. W13 -31.56 HIS534 HIS534

Biological activity:
The anti-mycobacterial activity of the synthesized derivatives was determined against the standard Mycobacterium smegmatis (NCIM No: 5138). The anti-mycobacterial activity of the synthesized derivatives was determined against the standard Mycobacterium smegmatis (NCIM No: 5138). Mycobacterium smegmatis is an organism belonging to Mycobacterium family having nearly about 80% genome similarity with Mycobacterium tuberculosis.Isoniazid is utilized as the positive standard for the anti-mycobacterial activity. Minimum inhibitory concentration (MIC) of the all-23 derivatives are summarized in Fig 7. All the compounds have shown good to moderate activity against the tested strain. Compound R 26, Q30 and M9 are showed maximum antitubercular activity (MIC: 62.5 μgm/ml). Excellent activity of the M9 and R 26 indicates halogens are having the positive effect on the antitubercular activity, which activity of Q30 is interesting finding which indicates substitution of the heterocyclic nucleus will also potentiate the activity. Derivative L13 showed good activity (MIC: 125μgm/ml), which justifies the substitution of halogen in the aromatic ring. A10, C13, F1, O13, O17, Q21, Q22, Q24, R25, R6, U8, and W13 are moderately active compounds with (MIC: 500μgm/ml).

DISCUSSION AND CONCLUSION: Conclusion:
Attempts to design and develop molecules targeting secretory systems of Mycobacterium tuberculosis yielded following significant findings. Identification and validation of secretory systems as targets for anti-tubercular drug design and discovery has been successfully carried out. Out of three protein export systems associated with Mycobacterium tuberculosis SEC protein export system has been utilized successfully for the development of antitubercular against which are selective and can be utilized against all resistant form of tuberculosis. Protein export systems are conserved systems and they are not having any isoform in human so targeting protein export systems will be the potential route for development of selective and active antitubercular agents. Pocket modeling of the active site or binding site of SEC revealed the interesting fact about size and shape of the binding pocket of SEC and which signified the development of hydrophobic ligands for binding with SEC of Mycobacterium tuberculosis. Based on pocket modeling data and Literature survey total 5184 molecules were designed around thiazole scaffold via the change in the different aromatic benzaldehyde structures. 5625 designed molecules were further scrutinized via Lipinski drug-like properties and toxicity profile using OCHEM and for binding efficiency using molecular docking analysis. Results of above all three analysis yielded 23 potent, selective molecules which are successfully synthesized via reaction of an aromatic aldehyde, thiosemicarbazide and thioglycolic acid. All the molecules are successfully synthesized using microwave assisted synthesis which improved the yield and reduced to the time of reaction than the procedures reported in the literature. All the synthesized 23 derivatives were characterized via all physicochemical methods, Melting point and IR, and NMR spectroscopy. Halogen substituted derivatives showed significant activity which indicates substitution of an electron withdrawing group in aryl ring will potentiate anti-mycobacterial activity. M26, U8 and R26 molecules have significant desirable biological activity and specific interactions with SEC, Further optimization of these leads is necessary for the development of potential antitubercular drug like candidates. These potential drug candidates with specific SEC inhibitory properties have resulted from the utilization of integration of pocket modeling and virtual screening.

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GİRİŞ ve AMAÇ: Kokleada dahil olmak üzere mikrodolaşım ve hemodinamik bozukluklar, diyabetli hastalarda yaygın olarak görülür. Diyabetik sıçanlar üzerine yapılan bir çalışma, dıştaki saç hücrelerindeki histopatolojik değişiklikleri, sarmal gangliyon ve kulaktaki mitokondriyal hasarı ortaya koymuştur. Hiperglisemi, Protein Kinaz C (PKC) aktivasyonunu artırabilir. Bir antioksidan olan Kürkümin, PKC ve Ca2+ düzenini de etkiler. Bu çalışmanın amacı, diyabetik sıçanlarda koklear fibroblastlarda PKK ekspresyonlarının azaltılmasında kürküminin rolünü öğrenmektir.
YÖNTEM ve GEREÇLER: 24 adet Wistar sıçanı üzerinde 6 gruba ayrılmış deneysel bir çalışma. Grup 1: kontrol grubu; Grup 2: kürkümin uygulaması olmayan diyabetik grup; Grup 3 ve 4: kürkümin uygulaması olan diyabetik gruplar (sırasıyla 3 gün süreyle 200 mg/kgbw ve 400 mg/kgbw); Grup 5 ve 6: kürkümin uygulaması olan diyabetik gruplar (sırasıyla 8 gün boyunca 200 mg/kgbw ve 400 mg/kgbw). Koklear dokular tüm gruplardan alındı ve immünohistokimyasal olarak boyandı ve PKC ekspresyon skorları, Tek Yönlü ANOVA (0.05'lik önem derecesi) ile analiz edildi.
BULGULAR: Grup 1 ile grup 2, grup 2 ve grup 3, 4, 5, 6 arasında PKC ekspresyonlarında önemli farklılıklar bulundu (p<0.05). Farklı dozlar ve kürküminin uygulama süresi ile ilgili olarak PKC ekspresyonunda önemli bir fark yoktu.
TARTIŞMA ve SONUÇ: Kürkümin, diyabetik sıçanların koklear fibroblastlarındaki PKC ekspresyonlarını azaltabilir.

INTRODUCTION: Microcirculation and hemodynamic disturbances, including in the cochlea, are commonly found in diabetic patients. A study on diabetic rats discovered the histopathological changes in outer hair cells, spiral ganglion and mitochondrial damage in the ear. Hyperglycemia can increase the activation of Protein Kinase C (PKC). Curcumin as an antioxidant also affects the regulation of PKC and Ca2+. The aim of this study is to learn the role of curcumin in decreasing the PKC expressions in the cochlear fibroblasts of diabetic rats.
METHODS: An experimental study on 24 Wistar rats divided into 6 groups. Group 1: control group; group 2: diabetic group without curcumin administration; group 3 and 4: diabetic groups with curcumin administration (200 mg/kgbw and 400 mg/kgbw for 3 days, respectively); group 5 and 6: diabetic groups with curcumin administration (200 mg/kgbw and 400 mg/kgbw for 8 days, respectively). Cochlear tissues were taken from all groups and immunohistochemistry-stained, and the PKC expression scores were analysed with One-Way ANOVA (a significance level of 0.05).
RESULTS: Significant differences in PKC expressions (p<0.05) were found between group 1 and group 2, group 2 and group 3, 4, 5, 6. There was no significant difference in PKC expression regarding the different doses and the duration of curcumin administration.
DISCUSSION AND CONCLUSION: Curcumin can reduce the PKC expressions in the cochlear fibroblasts of diabetic rats.

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INTRODUCTION: Polymeric nanoparticles is a promising novel drug delivery system and have advantageous in cancer therapy. Etoposide is an anticancer agent that is used in the treatment of a variety of malignancies. The present study was aimed to prepare and evaluate the Novel polymeric nanoparticles containing etoposide.
METHODS: 32 full factorial design was used to study the effect of Eudragit EPO and Pluronic F-68 on characterization of nanoparticles suspension. The polymeric nanoparticles was prepared by nano-precipitation technique. The prepared nanoparticles was evaluated by percentage yield, drug polymer compatibility using FTIR and DSC analysis, drug content, entrapment efficiency, zeta potential, particle size, SEM, XRD, In-vitro drug release studies, kinetic modeling, stability studies and in-vivo animal study. Response surface plots were studied which was generated using PCP dissolution software.
RESULTS: Scanning electron microscopic studies confirmed their porous structure with number of nanochannels. The FTIR spectra showed stable character of etoposide in mixture of polymers and revealed the absence of drug polymer interactions. DSC study revealed that drug was involved in complexation with nanoparticles. The average particle size of etoposide nanoparticles was found to be in the range of 114.4 nm to 136.7 nm. The results of zeta potential values were attained to ensure a good stability of nanosuspensions. In-vitro release of drug from nanoparticles follows peppas and showed controlled release behavior for a period of 24 h. The optimized nanoparticles were subjected to stability studies at 4ºC in refrigerator and found most suitable temperature for storage of Etoposide nanoparticles. The average targeting efficiency of drug loaded nanoparticles was found to be 41.88 ±0.030% of the injected dose in liver, 25.66±0.320% in spleen 13.82±0.090% in lungs, 4.52±0.300% in kidney and 4.18±0.490% in brain.
DISCUSSION AND CONCLUSION: The study concluded that etoposide nanoparticles could be effective in sustained release and the drug loaded nanoparticles.

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GİRİŞ ve AMAÇ: Bu çalışmanın amacı Vaccinium arctostaphylos (V. arctostaphylos) L.’den hazırlanan etanol (EE), metanol (ME) ve su (AE) ekstraktlarının toplam fenolik, antosiyanin, flavonoit içerikleri ve biyolojik özelliklerinin incelenmesidir.
YÖNTEM ve GEREÇLER: V. arctostaphylos’un EE, ME ve AE ekstraktları hazırlandı. Bu ekstraktların total fenolik, antosiyanin ve flavonoid içerikleri, antioksidan (DPPH, metal iyon şelatlama ve FRAP metotları), α-glukozidaz, anti-inflamatuvar ve DNA koruma özellikleri araştırılmıştır.
BULGULAR: EE, 44.42 ± 1.22 mg GAE/g kuru ağırlık, 8.46 ± 0.49 mg/CGE/g kuru ağırlık ve 9.22 ± 0.92 mg QEE/g kuru ağırlık değerleriyle en yüksek toplam fenolik, antosiyanin ve flavonoid içeriğine sahip olduğu görülmüştür. Bununla birlikte ekstraktların antioksidan aktiviteleri sırasıyla EE > ME > AE olduğu belirlendi. EE ve ME α-glukozidaz enzimini sırasıyla 0.301 ± 0.002 mg/mL ve 0.477 ± 0.003 mg/mL IC50 değerleriyle inhibe etmiştir. Ayrıca, EE ve ME’nin inhibisyon sabiti (Ki) değerleri 0.48 ± 0.02 mg/mL ve 0.46 ± 0.01 mg/mL bulunarak, yarışmasız inhibisyon gerçekleştirdikleri belirlenmiştir. EE’nin 100 ve 300 mg/kg dozları farelerde formalin ile indüklenen ödemi önemli derecede azalttığı belirlenmiştir. DNA koruma çalışmalarında, ekstraktlar radikal süpürme aktivitesinden dolayı Fenton reaktifiyle oluşturulan hasara karşı süpersarmal plasmid pBR322 DNA’yı korumuştur.
TARTIŞMA ve SONUÇ: Sonuçlarımız, V. arctostaphylos L.'nin EE'sinin güçlü antioksidan, anti-inflamatuar, α-glukozidaz inhibisyon ve DNA koruyucu etkilere sahip olduğunu göstermiştir; bu, oksidatif hasar ve iltihaplanma ile ilişkili hastalıkları önlemek veya tedavi etmek için etkili bir tıbbi bitki olabileceğini düşündürmektedir.

INTRODUCTION: The scope of this study was to investigate total phenolic, anthocyanin, flavonoid contents and biological properties of ethanol extract (EE), methanol extract (ME) and aqueous extract (AE) from Vaccinium arctostaphylos (V. arctostaphylos) L.
METHODS: EE, ME and AE of V. arctostaphylos were prepared. Various biological activities such as total phenolic, anthocyanin and flavonoid contents, antioxidant (DPPH, ferrous ion-chelating and FRAP assays), α-glucosidase inhibitory, anti-inflammatory and DNA protective properties of these extracts were studied.
RESULTS: EE exhibited the highest total phenolic, anthocyanin and flavonoid contents with 44.42 ± 1.22 mg GAE/g dry weight, 8.46 ± 0.49 mg/CGE/g dry weight and 9.22 ± 0.92 mg QEE/g dry weight, respectively. The antioxidant activities of extracts followed order: EE > ME > AE. EE and ME inhibited α-glucosidase enzyme and their IC50 values were 0.301 ± 0.002 mg/mL and 0.477 ± 0.003 mg/mL respectively. In addition, EE and ME were determined as noncompetitive inhibitor with the inhibitory constant (Ki) values of 0.48 ± 0.02 mg/mL and 0.46 ± 0.01 mg/mL. 100 and 300 mg/kg doses of EE caused a significant reduction in formalin-induced edema in mice, demonstrating anti-inflammatory effect of EE. In DNA protective studies, all of extracts prevented supercoiled plasmid pBR322 DNA against damage caused by Fenton’s reagents due to their radical scavenging activities.
DISCUSSION AND CONCLUSION: Our results demonstrated that EE of V. arctostaphylos L. had strong antioxidant, anti-inflammatory, α-glucosidase inhibitory and DNA protective effects, suggesting that it might be effective medical plant to prevent or treat diseases associated with oxidative damage and inflammation.

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GİRİŞ ve AMAÇ: Saxagliptin ve dapagliflozin'in sabit doz kombinasyonu antidiyabetik ilaç tedavisi için onaylanmıştır ve Qtern markası ile pazarda yer almaktadır.Bu çalışmada amaç, insan plazmasındaki Saxagliptin ve dapagliflozin'in eş zamanlı tayini için US-FDA klavuzlarına uygun şekilde linagliptin iç standardı kullanarak ve basit, hızlı, hassas ve validasyonu yapılmış izokroatik ters faz yüksek performanslı sıvı kromatografi (RP-HPLC) yöntemi geliştirmektir.
YÖNTEM ve GEREÇLER: Method 4'lü akış pompasına sahip Waters 2695 marka HPLC cihazı ile gerçekleştirilmiştir. Analitin ayrılmasında Eclipse XDB C18 kolon (150 X 4.6µm x 5mm) kullanılmıştır. Kullanılan mobil fazın bileşimi ise pH 5.0' e ayarlanmış %0.1 orto fosforik asit ve asetonitril (50: 50) şeklinde olup akış hızı analiz süresince 1 ml/dk'dır.
BULGULAR: Analit 254nm'de tayin edilmiştir. İç standart, saxagliptin ve dapagliflozin'in alıkonma zamanları sırasıyla 2.746, 5.173 ve 7.218dk olarak tespit edilmiştir. Pikler interferanslar gözlenmeden elde edilmiştir. Metot validasyonu saxagliptin ve dapagliflozin için sırasıyla 0.01 ile 0.5µg/ml ve 0.05 ile 2µg/ml doğrusal derişim aralığında 0.998 korelasyon katsayısı ile gerçekleştirilmiştir. Numunlere ait 6 ölçüme ait kesinlik ve doğruluk tayin sınırları içerisinde bulunmuştur. Analitlerin insan plazması içinde -28ºC sıcaklıkta 37gün boyunca kararlı halde kaldığı belirlenmiştir.
TARTIŞMA ve SONUÇ: Bu yönteme ait elde edilen kararlılık, duyarlılık, özgüllük ve tekrarlanabilirlik sonuçları, geliştirilen bu yöntemin insan plazmasında saxagliptin ve dapagliflozin'in belirlenmesi için uygun olduğunu ortaya koymuştur.

INTRODUCTION: The fixed dose combination of saxagliptin and dapagliflozin, recently approved antidiabetic medication. It is marketed with a brand name Qtern. The intend method aim to develop a simple, rapid, sensitive and validated isocratic reversed phase high performance liquid chromatography (RP-HPLC) method for the simultaneous estimation of saxagliptin and dapagliflozin in human plasma by using linagliptin as internal standard as per US-FDA guidelines.
METHODS: The method was performed on Waters 2695 HPLC equipped with quaternary pump. The analyte separation was achieved using Eclipse XDB C18 (150×4.6µ×5mm) column with a mobile phase consisting of 0.1% ortho phosphoric acid and acetonitrile (50: 50) with pH adjusted to 5.0 at1ml/min flow rate.
RESULTS: The analyte was detected at 254nm. Retention time of the internal standard, saxagliptin and dapagliflozin was found at 2.746, 5.173 and 7.218minutes, respectively. The peaks were found to be free of interference. The method is validated over a dynamic linear range of 0.01 to 0.5µg/ml and 0.05 to 2µg/ml for saxagliptin and dapagliflozin, respectively, with a correlation coefficient of 0.998. The precision and accuracy of samples of six replicate measurements at LLOQ level was within limit. The analytes were found to be stable in human plasma at -28°C for 37 days.
DISCUSSION AND CONCLUSION: The stability, sensitivity, specificity and reproducibility of this method make it appropriate for the determination of saxagliptin and dapagliflozin in human plasma.

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GİRİŞ ve AMAÇ: Gypsophila türleri, tıbbi ve ticari açıdan çok önemlidirler ve ilginç doğal maddeler içerirler. Bununla birlikte, literatürde Gypsophila türlerinin uçucu yağ ve yağ asidi bileşimi hakkında herhangi bir çalışma bulunmamaktadır. Bu nedenle Gypsophila laricina Schreb.'nın uçucu yağ ve yağ asidi bileşimi araştırılmasına karar verilmiştir.
YÖNTEM ve GEREÇLER: Bitki materyali çiçeklenme döneminde toplanılmıştır. Gypsophila laricina Schreb. türünün toprak üstü kısmının uçucu yağ bileşimleri gaz kromatografi ve gaz kromatografi-kütle spektrometresi (GC-MS) aracılığıyla analiz edilmiştir. Yağ asit bileşimleri gaz kromatografi-kütle spektrometresi (GC-MS) aracılığıyla analiz edilmiştir.
BULGULAR: G. laricina Schreb. uçucu yağlarında altmış altı bileşik ve yağ asidlerinde on bileşik tespit edilmiştir. Uçucu yağın ana bileşenleri heksadekanoik asit (27.03%) ve hentriakontan (12.63%) olarak belirlenmiştir. Yağ asidinin ana bileşenleri ise (Z,Z)-9,12-oktadekadienoik asit metil ester (18: 2) 40.4%, (Z)-9-octadesenoik asit metil ester (18: 1) 35.0% ve heksadekanoik asit metil ester (16: 0) 13.0% olarak tespit edilmiştir.
TARTIŞMA ve SONUÇ: Bitki yağ asidi bileşiminin çoklu doymamış yağ asitleri bakımından zengin olduğu saptanmıştır. Bitki uçucu yağının yüksek oranda n-alkan ve yağ aside türevleri içerdiği belirlenmiştir. Bu araştırmadan elde edilen sonuçların, Gypsophila türlerinin kimyası üzerine yapılacak daha ileri araştırmalara katkı sağlayacağı düşünülmektedir.

INTRODUCTION: Gypsophila species have very high medicinal and commercial importance and also contains interesting natural substances. However, there is no report on the essential oil and fatty acid composition of any Gypsophila species. This prompted us to investigate the essential oil and fatty acid composition of Gypsophila laricina Schreb.
METHODS: Plant materials were collected during the flowering period. Essential oil composition of aerial parts of Gypsophila laricina Schreb. were analysed by gas chromatography and gas chromatography-mass spectrometry. And the fatty acid compositions were analysed by gas chromatography-mass spectrometry.
RESULTS: Sixty-six and ten compounds were identified in the essential oil and fatty acid of G. laricina Schreb. respectively. The major components of the essential oil were hexadecanoic acid (27.03%) and hentriacontane (12.63%). The main compounds of the fatty acid were (Z,Z)-9,12-octadecadienoic acid methyl ester (18: 2) 40.4%, (Z)-9-octadecenoic acid methyl ester (18: 1) 35.0 % and hexadecanoic acid methyl ester (16: 0) 13.0%.
DISCUSSION AND CONCLUSION: The result showed that the fatty acid composition are rich in polyunsaturated fatty acids. The essential oils of G. laricina Schreb. were dominated by fatty acid derivatives and n-alkanes. We believe the results obtained from this research will stimulate further research on the chemistry of Gypsophila species.

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GİRİŞ ve AMAÇ: Bu çalışmanın amacı, üzerinde daha önce herhangi bir fitokimyasal çalışma bulunmayan Heracleum pastinaca’ nın sekonder bileşiklerinin izolasyonu ve karakterizasyonudur.
YÖNTEM ve GEREÇLER: Maddelerin izolasyon prosedürleri klasik kromatografik metodlara göre yapılmıştır. Saf bileşiklerin yapıları, MS deneyleri ile 1D ve 2D NMR spektroskopik analizleri kullanılarak aydınlatılmış; literatür verileriyle de doğrulanmıştır.
BULGULAR: Heracleum pastinaca Fenzl.’ in tüm kısımlarının ilk defa fitokimyasal açıdan incelenmesinde, yedi adet bilinen; izokersetin (1), rutin (2), afzelin (3), astragalin (4), izoramnetin 3-O-glukozit (5), nikotiflorin (6) ve narkisozit (7) isimli flavonoit glikozileri izole edilerek tanımlanmıştır
TARTIŞMA ve SONUÇ: Bu çalışma ile izole edilen flavonoitlerin tamamı, H. pastinaca’ dan, 3, 5, 6, 7 nolu bileşikler ise Heracleum cinsinden ilk defa tanımlanmıştır.

INTRODUCTION: The objective is the study to isolate and characterize the secondary metabolites of Heracleum pastinaca which has not been previously investigated.
METHODS: Conventional chromatographic procedures were carried out for isolation of the compounds. The structures of the compounds were elucidated by extensive 1D and 2D NMR spectroscopic analysis in combination with MS experiments and comparing with relevant litearature data
RESULTS: The first phytochemical investigation on the whole parts of Heracleum pastinaca Fenzl. led to the isolation and identification of seven known flavonoid glycosides; isoquercetin (1), rutin (2), afzelin (3), astragalin (4), isorhamnetin 3-O-glucoside (5), nicotiflorine (6) and narcissoside (7).
DISCUSSION AND CONCLUSION: This is the first report on the isolation of these flavonoid glycosides from H. pastinaca and compounds 3, 5, 6 and 7 from genus Heracleum.

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INTRODUCTION: Present investigation was aimed at developing the solid dispersion of itraconazole (ITR) using sacrificial excipients like pregelatinized starch, spray dried lactose alongside HPMC E5 and Poloxamer 188, thereby arresting the conversion of amorphous form of ITR to crystalline form and to assess the dissolution stability of an amorphous form of the drug on short-term storage.
METHODS: Itraconazole loaded solid dispersions were prepared by kneading method. Formulation optimization was achieved by using 24 full factorial design on the basis of cumulative percent drug released at t30, t60 and t120 min. Artificial neural network (ANN) was also applied as a statistical tool for obtaining better predictive ability and the outcomes of ANN were compared with that of design expert software.
RESULTS: The spectral data revealed no drug-carrier interactions. The P-XRD study of optimized batch showed decrease in crystallinity of drug as compared to the untreated drug. The in vitro dissolution studies of the optimized batch showed highest dissolution (92% at 120 min.) in comparison to the other formulations. Dissolution stability study of was performed at 40ºC and 75% RH for 90 days for the optimized formulation. Results of optimized batch showed insignificant changes in cumulative percentage drug release on storage.
DISCUSSION AND CONCLUSION: Dissolution stability could be attributed to the presence of sacrificial excipients as they tend to absorb the moisture on storage and possibly itself get converted into crystalline form thereby minimizing the recrystallization of ITR.

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GİRİŞ ve AMAÇ: Nonsteroidal antienflamatuvar ilaç etken maddesi tenoksikamın (TX) elektro-oksidasyon davranışı çok duvarlı karbon nanotüple (MWCNTs) modifiye edilmiş camsı karbon elektrot (GCE) ile dönüşümlü voltametri (CV), diferansiyel puls voltametri (DPV) ve kare dalga voltametri (SWV) ile çalışıldı.
YÖNTEM ve GEREÇLER: Camsı karbon elektrot, TX’in voltametrik metodlarla hassas tayini için MWCNTs ile modifiye edildi.
BULGULAR: Potansiyel pozitif yönde tarandığında TX’in pik akımı 0.520 V civarinda DPV ile, 0.570 V civarında SWV ile oluştu. TX’in oksidasyon prosesi tersinmez ve difüzyon kontrollü davranış gösterdi. DPV ve SWV için doğrusal cevaplar sırasıyla 2 × 10-7- 1 × 10-5 M, 1.43 × 10-9 M yakalama alt sınırı (YAS) ile, 8 × 10-9 - 8 × 10-6 M, 9.97 × 10-10 M YAS ile 1 M asetat tamponu pH 5.5 içinde elde edildi.
TARTIŞMA ve SONUÇ: Tamamen valide edilmiş DPV ve SWV başarılı bir şekilde TX’in farmasötik dozaj formundan miktar tayini için uygulandı ve memnun edici sonuçlar elde edildi.

INTRODUCTION: The electro-oxidation behavior of nonsteroidal anti-inflammatory drug tenoxicam (TX) was studied on multiwalled carbon nanotubes (MWCNTs) modified glassy carbon electrode (GCE) by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and square wave voltammetry (SWV).
METHODS: GCE was modified with MWCNTs for sensitive determination of TX with voltammetric methods.
RESULTS: The current peaks for TX occurred at around 0.520 V for DPV and 0.570 V for SWV when the potential was scanned in the positive direction. The oxidation process of TX has shown irreversible and diffusion controlled behavior. The linear responses have been obtained in the range from 2 × 10-7 to 1 × 10-5 M with the limit of detection (LOD) 1.43 × 10-9 for DPV and from 8 × 10-9 to 8 × 10-6 with the LOD 9.97 × 10-10 for SWV in 1 M acetate buffer solution at pH 5.5.
DISCUSSION AND CONCLUSION: Fully validated DPV and SWV were successfully applied for the determination of TX from pharmaceutical dosage form and obtained satisfying results.

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GİRİŞ ve AMAÇ: Giriş: Nörolojik kesimlerin tedavisinde Rho (serin / treonin) kinazların rolünü anlamak için, Rho enziminin güçlü kısıtlayıcılarını 2D niceliksel yapı aktivitesi ilişkisi (QSAR) modeliyle bulmak için girişimlerde bulunulmuştur.
YÖNTEM ve GEREÇLER: Gereç ve Yöntemler: QSAR çalışmaları, kimyasal olarak modellenmiş modeli oluşturmak üzere hizalanan anilinler ve benzilamin analoglarından üre bazlı iskele üzerinde yürütülmüştür. Modelin oluşturulması için çoklu doğrusal regresyon, kısmi en küçük kareler ve yapay sinir ağı gibi doğrusal ve doğrusal olmayan analizleri içeren çok değişkenli istatistiksel yaklaşımlar uygulanmış ve ayrıca Amaçlanan moleküllerin ilaç benzeri özelliklerinin saptanması için (in silico?) ADME çalışmaları uygulanmıştır.
BULGULAR: Bulgular: Ligand temelli analizler uygulanmış ve S-değeri = 0.38, F-değeri = 48.41, r = 0.95, r² = 0.91 ve r²cv = 0.86 gibi mükemmel istatistiksel yöndedir. Beş aydınlatıcı değişken, VAMP polarizasyon YY bileşeni (tüm molekül), VAMP dipol Y bileşeni (tüm molekül), VAMP dipol Z bileşeni (tüm molekül), Kier ChiV6 yol indeksi (tüm molekül) ve atalet momenti 2 boyutu (tüm molekül) idi Bileşiklerin potensi üzerinde bulunmuş ve kendi üzerinde büyük etkisi vardır.
TARTIŞMA ve SONUÇ: Tartışma ve Sonuç: Standart istatistiksel parametrelerin değerleri, bu modelin öngörücü gücü ve dayanıklılığını ortaya koymakta ve aynı zamanda beş tanımlayıcıya verilen önemi değerli bilgiler sağlamaktadır. Edinilen fizyolojik özellikler (elektronik, topolojik ve sterik), Rho kinaza karşı aktivite için gerekli olan önemli yapısal özellikleri gösterir. Lipinski'nin üre bazlı türevleri üzerindeki beş kuralını uyguladıktan sonra hiçbir kural bu kuralları ihlal etmedi. Dolayısıyla, bu özellikler, aktif nörolojik ajanların yeni Rho-Kinaz inhibitörleri olarak modellenmesi ve taranmasında etkili bir şekilde kullanılabilir.

INTRODUCTION: Introduction: Understanding the role of Rho (serine/threonine) kinases in the treatment of neurological segments, attempts have been made to find potent inhibitors of Rho enzyme by 2D quantitative structure activity relationship (QSAR) model.
METHODS: Materials and Methods: QSAR studies were executed on urea based scaffolds from anilines and benzylamines analogs, which were aligned for generation of chemometric based model. Multivariate statistical approaches have been applied includes linear and non-linear analysis such as multiple linear regression, partial least square and artificial neural network for the generation of model, and also an application of ADME studies was performed to ascertain the novelty and drug like properties of the intended molecules.
RESULTS: Results: Ligand based analysis have been implemented and having excellent statistical relevance such as S-value= 0.38, F-value= 48.41, r= 0.95, r²= 0.91 and r²cv= 0.86. Five illuminating variables, VAMP polarization YY component (whole molecule), VAMP dipole Y component (whole molecule), VAMP dipole Z component (whole molecule), Kier ChiV6 path index (whole molecule) and Moment of inertia 2 size (whole molecule) were found and own profound influence on the potency of the compounds.
DISCUSSION AND CONCLUSION: Discussion and Conclusion: The values of standard statistical parameters reveal the predictive power and robustness of this model and also provided valuable insight to the significance of five descriptors. The acquired physicochemical properties (electronic, topological and steric) shows the important structural features required for activity against Rho kinase. After performing Lipinski’s rule of five on urea based derivatives no molecule were violating the rule. So, these features can be effectively employed for modeling and screening of active neurological agents as novel Rho-Kinase inhibitors.

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INTRODUCTION: Co-processing technique has been utilized to develop excipients of improved or/and desired functionalities. Silicified MCC (Prosolve), cellactose and Avicel CE-15 are commercially available co-processed excipients which have improved flow and consolidation properties. One of the major limitations challenging co-processing technique is the fixed ratio of the excipients in a co-processed mixture which may not be an optimum choice for the active ingredient (s) and the dose per a formulation under development.
Trials were made to co-process excipients to manufacture direct compression MZ tablets.
The objective of this work was to co-process and evaluate the tableting properties of (MCR), a new cellulose-based tableted excipient produced from the slugs from the granules of CMCC/CRC. Metronidazole a model of non-freely flowing incompressible API was employed to evaluate MCR for the production of direct compression MZ tablets.


METHODS: Methods: Processing and evaluation of CMCC and CRC: CMCC and CRC were processed and evaluated for their physico-chemical properties.
Processing of MCR: MCR was produced by sifting the slugs of 4: 1 CMCC/CRC granules made with alcohol.. MCR was characterized and evaluated and used to compress MZ tablets.
Evaluation of MZ tablets: The produced MZ tablets were evaluated for their physico-chemical properties.

RESULTS: CMCC and CRC were successfully processed and the prepared MCR was successfully co-processed. The compressed MZ tablets were evaluated. Their mechanical properties and disintegration and dissolution behaviors were satisfactory. MCR was sensitive to magnesium stearate (MS) and moisture.
DISCUSSION AND CONCLUSION: MCR proved to be a direct compression excipient of adequate
tableting properties. Tablets of accepted mechanical properties and fast disintegrating and dissolving rates were produced. MCR is recommended to be applied as a direct compression excipient. It is unfortunately sensitive to MS and moisture which may limit its use

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GİRİŞ ve AMAÇ: Enzim izolasyonu ve enzimler üzerinde yapılan deneyler, büyük çaba, maliyet ve zaman gerektirir. Bu yüzden, enzimlerin kullanılabilirliğinin immobilizasyon ile uzatılması önemlidir. Bu çalışmadaki amacımız, aldoz redüktaz (AR) enzimini immobilize etmek ve serbest AR’ninkiler ile karşılaştırarak immobilize AR’nin deney şartlarını optimize etmektir.
YÖNTEM ve GEREÇLER: AR, sığır karaciğer ve böbreğinden izole edildi ve gluteraldehid ile fotoğrafik jelatine çapraz bağlanarak immobilize edildi. Daha sonra, enzim aktivitesi belirlenerek serbest ve immobilize AR’nin optimum pH, sıcaklık ve depolama koşulları tespit edildi.
BULGULAR: Serbest AR için pH 7,0 ve 60 °C olan optimum pH ve sıcaklık seviyeleri, immobilizasyondan sonra pH 7,5 ve 50 °C olarak belirlendi. İmmobilize AR’nin enzim aktivitesinin, 15 kez kullanımdan sonra %65 oranında korunduğu tespit edildi. Bununla birlikte, +4°C’de 20 gün boyunca saklanan serbest AR’nin aktivitesi %85 oranında korunurken immobilize AR’nin aktivitesinin %95 oranında korunduğu bulunmuştur.
TARTIŞMA ve SONUÇ: Deneylerimiz, immobilizasyonu takiben enzim aktivitesini etkileyen koşulların değişebileceğini göstermektedir. Ayrıca, immobilize AR, serbest AR’ye göre daha yüksek aktiviteyle korunup tekrar tekrar kullanılabilmektedir.

INTRODUCTION: Isolation of enzymes and experiments on enzymes require a great effort and cost and also they are time-consuming. Therefore, it is important to extend the usability of the enzymes by immobilizing. In this study our purpose was to immobilize the aldose reductase (AR) enzyme and to optimize the experimental conditions of the immobilized AR and compare them to the free AR’s.
METHODS: AR was isolated from bovine liver and immobilized the enzyme into the photographic gelatin by cross-linking with glutaraldehyde. Then the optimum conditions of free and immobilized AR for pH, temperature and storage were characterized by determining the enzyme activity.
RESULTS: Following immobilization, the optimum pH and temperature levels of free AR which were pH 7.0 and 60 °C slightly altered to pH 7.5 and 50 °C. The enzyme activity of the immobilized AR maintained for about 65% after reusing 15 times. Moreover, immobilized AR can maintain its original activity for 95% after 20 days storing at 4 °C, while the retained activity of the free AR was 85% of its original activity.
DISCUSSION AND CONCLUSION: Our experiments indicated that the conditions which affect the enzyme activity might alter following immobilization. Once the optimum experimental conditions are fixed, the immobilized AR can be stored and reused with a higher efficiency than the free aldose reductase. Moreover, this study provides an insight into the advantages of using immobilized AR in the enzyme assays rather than the free one.

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GİRİŞ ve AMAÇ: Bu çalışmada Türkiye yetişen beş Lathyrus türü, L. armenus, L. aureus, L. cicilicus, L. laxiflorus subsp. laxiflorus ve L. pratensis türlerinin metanollü ekstreleri ve hekzan, etil asetat, kloroform ve su fraksiyonların antimikrobiyal ve antienflamatuar aktivitesi değerlendirilmiştir.
YÖNTEM ve GEREÇLER: Ekstrelerin ve fraksiyonların antimikrobiyal aktivitesi Staphylococcus aureus ATCC 29213, Bacillus subtilis ATCC 6633, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 ve Candida albicans ATCC 10231 karşı elde edilmiştir. In vitro antienflamatuar ise insan kırmızı kan hücresi kullanarak membran stabilizasyon yöntemi ile değerlendirilmiştir.
BULGULAR: Etil asetatlı fraksiyonlar diğer ekstre ve fraksiyonlara göre daha yüksek antimikrobiyal aktivite, sulu fraksiyonlar ise diğer ekstre ve fraksiyonlara göre daha yüksek antienflamatuar aktivite göstermiştir. Ayrıca, L. pratensis'in su fraksiyonu, standart olarak kullanılan asetilsalisilik asit ve diklofenak sodyumdan daha yüksek anti-inflamatuar aktivite göstermiştir
TARTIŞMA ve SONUÇ: Elde edilen sonuçlara göre Lathyrus türlerinin ekstreleri ve fraksiyonlarının membran stabilizasyon aktiviteye sahip olup, ve in vivo anti-inflamatuar aktivite deneyleri için bir ön çalışma olabileceğini belirtmiştir.

INTRODUCTION: The present study aimed to evaluate antimicrobial and anti-inflammatory activities of methanol extracts and n-hexane, ethyl acetate, chloroform and water fractions of five Lathyrus species, L. armenus, L. aureus, L. cicilicus, L. laxiflorus subsp. laxiflorus and L. pratensis growing in Turkey.
METHODS: The antimicrobial activities were screened against Staphylococcus aureus ATCC 29213, Bacillus subtilis ATCC 6633, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 and Candida albicans ATCC 10231. Broth dilution method was used to determine the antimicrobial activities of extracts and fractions. In vitro anti-inflammatory activity of these extracts and fractions were determined by using human red blood cell (HRBC) membrane stabilization method.
RESULTS: The results demonstrated that ethyl acetate fractions of the tested species exhibited higher antimicrobial activity than the other extracts. Among all of the tested extracts and fractions, the highest anti-inflammatory activity was detected in water fractions. Furthermore, water fractions of L. pratensis showed better anti-inflammatory activity than acetylsalicylic acid and diclofenac sodium which were used as standard drugs in this assay.
DISCUSSION AND CONCLUSION: The results point out that the membrane stabilizing effect of the various extracts and fractions of the Lathyrus species and could be a preliminary study for in vivo anti-inflammatory activity experiments.

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Multiple sclerosis (MS) is the most common cause of neurologic disability in adults worldwide. Two main issues have caused MS patients to face several problems. One issue is that the definite cause of MS has not yet been determined and the other issue is the lack of a definite treatment for this disease. The people with MS, therefore, seek out complementary and alternative medications to manage the symptoms of this disease. Meanwhile, medicinal plants have been demonstrated to have possible positive pharmacological effects in treating MS in different models. The reliable articles indexed in the databases Web of Science, Scopus, PubMed Central, PubMed, Scientific Information Database, and Institute for Scientific Information were retrieved and analyzed to conduct this review. Medicinal plants and plant compounds caused decrease in the neurologic deficits due to MS. Clinical evidence has demonstrated the clinical potential of Cannabis sativa extract, cannabinoids, Ginkgo biloba, beta-phytosterol, and Lippia citriodora extract to improve MS symptoms. These plants and compounds can also improve spasticity, muscle spasm, neuropathic pain, and urinary tract complications in at least some of these patients. Nanocurcumins and Punica granatum L peel extract have exhibited positive effects on animal models and can decrease neurologic deficits by reducing inflammation. Medicinal plants and their compounds can serve as new sources of MS drugs because they can improve MS symptoms.

GİRİŞ ve AMAÇ: Akt, antikanser ilaç keşfinde ve gelişiminde önemli bir hedef olarak düşünülmektedir ve bu nedenle Akt’ı hedefleyen yeni potent antikanser ajanların keşfi için yoğun çaba harcanmıştır.
YÖNTEM ve GEREÇLER: Tiyadiazollerin antikanser ilaç keşfindeki önemine bağlı olarak, bu çalışmada sekiz adet 1,3,4-tiyadiazol türevinin C6 sıçan glioma ve A549 insan akciğer adenokarsinoma hücre dizileri üzerindeki sitotoksik etkileri MTT deneyi kullanılarak araştırılmıştır. En etkili antikanser ajanların apoptoz, kaspaz-3 aktivasyonu, mitokondriyal membran potansiyeli, hücre döngüsü arresti üzerindeki etkileri BD FACS Aria (I) akış sitometrisi ile belirlenmiştir. Akt aktivite, C6 ve A549 hücre dizilerinde ELISA kolorimetrik yöntem kullanılarak ölçülmüştür. 3 ve 8 no’lu bileşiklerin Akt enziminin (PDB kod: 3OW4) aktif bölgesindeki olası bağlanma biçimlerini araştırmak için Schrodinger’s Maestro moleküler modelleme programı kullanılmıştır.
BULGULAR: N-(4-Klorofenil)-2-[(5-((4-nitrofenil)amino)-1,3,4-tiyadiazol-2-il)tiyo]asetamit (3) ve N-(6-nitrobenzotiyazol-2-il)-2-[(5-((4-nitrofenil)amino)-1,3,4-tiyadiazol-2-il)tiyo]asetamit (8), C6 hücre dizisinde apoptozu ve hücre döngüsü tutuklanmasını Akt aktivitesi inhibisyonu aracılığıyla (sırasıyla %92.36 ve %86.52) indüklemişlerdir. Bu bileşiklerin docking sonuçları, gözlemlenen Akt inhibitor aktiviteden π-π etkileşimleri, hidrojen bağları ve tuz köprüsü oluşumunun sorumlu olduğunu belirtmektedir.
TARTIŞMA ve SONUÇ: In vitro ve docking çalışmalarına göre, 3 ve 8 no’lu bileşikler umut vaat eden antiglioma ajanlar olarak dikkat çekmektedirler.

INTRODUCTION: Akt is considered as an attractive target for anticancer drug discovery and development and therefore extensive efforts have been devoted to the discovery of new potent anticancer agents targeting Akt.
METHODS: Due to the importance of thiadiazoles for anticancer drug discovery, herein eight 1,3,4-thiadiazole derivatives were investigated for their cytotoxic effects on C6 rat glioma and A549 human lung adenocarcinoma cell lines using MTT assay. The effects of the most promising anticancer agents on apoptosis, caspase-3 activation, mitochondrial membrane potential, cell cycle arrest were determined on a BD FACS Aria (I) flow cytometer. Akt activity was measured in C6 and A549 cell lines using an ELISA colorimetric method. Schrodinger’s Maestro molecular modeling package was used to explore the possible binding modes of compounds 3 and 8 in the active site of Akt enzyme (PDB code: 3OW4).
RESULTS: N-(4-Chlorophenyl)-2-[(5-((4-nitrophenyl)amino)-1,3,4-thiadiazol-2-yl)thio]acetamide (3) and N-(6-nitrobenzothiazol-2-yl)-2-[(5-((4-nitrophenyl)amino)-1,3,4-thiadiazol-2-yl)thio]acetamide (8) induced apoptosis and cell cycle arrest in C6 cell line through the inhibition of Akt activity (92.36% and 86.52%, respectively). The docking results of compounds 3 and 8 indicated that π-π interactions, H bonds and salt bridge formations were responsible for the observed Akt inhibitory activity.
DISCUSSION AND CONCLUSION: According to in vitro and docking studies, compounds 3 and 8 stand out as promising antiglioma agents.

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INTRODUCTION: The objective of the present work was to contribute to the identification of the major phenolic compounds in the hydroalcoholic extract of Artemisia campestrisHPLC-DAD coupled with ESI-MS. In addition, HPLC-DAD-EC quantification of phenolic, flavonoid contents and hydroxycinnamic acid was carried out.Finally, the antioxidant capacity of the extract was also evaluated using ORAC assay.
METHODS: Liquid chromatography with diode array, and electrochemical detection
The High Performance Liquid Chromatography (HPLC) system used was a Thermo Finnigan (Surveyor, San Jose, CA, USA),equipped with an autosampler, pump, photodiode-array detector (PDA) and electrochemical detector (ED).Chromatographic separation of compounds was carried out on a Lichrocart RP-18 column (250 x 4 mm, particle size 5 µm, Merck). The electrochemical detector (ED) Dionex® performed signal measurements by integratedvoltammetry at potentialsbetween -1.0 v and 1.0 v with a scan time of 1.00s.


RESULTS: The HPLC method employed for the separation of phenolic components in the hydro-alcoholic extract of A. Campestris revealed a good separation ofthe majority of the compounds.Chromatograms at 280 nm are widely used to study phenolic compounds because absorption at thiswavelengthissuitable to detect a large number of such compounds. The maximum absorption wavelengths (λ max), and parent, aglycone, and fragment ion masses of the components detected in the aqueous extract of A. campestris are shown in Table 2, where the compounds are numbered according to their retention times (Rt) in the obtained chromatograms.


DISCUSSION AND CONCLUSION: In the current work, 11 phenolic compounds in the hydro-alcoholic extract of A. campestris were tentatively identified using HPLC-DAD-ESI-MS/MS technique. The identified compounds contained phenolic acid derivatives and flavonoids. Moreover, the hydro-alcoholic extract showed a noticeable antioxidant potential; this high activity may be due to the presence of phenolic compounds. In conclusion, A. campestris aerial parts are considered a promising source of naturally occurring antioxidant agents.

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