INTRODUCTION: Cnidoscolus aconitifolius (Mill.) I.M.Johnstone is a medicinal plant widely used in ethnomedicine for the treatment of cancer, and other diseases in parts of Nigeria
METHODS: The effects of the methanol extracts of the leaf, stem, and root barks were evaluated on the breast (MCF-7), and lung (NCI-H460) cancer cells at 1-250 µg/mL using SRB assay and the extracts were screened for phytochemicals using standard method. The active methanol extract of the leaf of C. aconitifolius was partitioned into aqueous and chloroform fractions.
RESULTS: The stem and root extracts showed no activity at the maximum concentration, while the leaf extract at 100 µg/mL showed a remarkable cell growth inhibition against breast (-14.50 ± 0.58), and lung cancer (+53.29 ± 4.57 %) in vitro. The extracts showed the presence of saponins, terpenes, cardiac glycosides, and phenolic compounds. Partitioning of the active leaf extract further enhanced its activity as the chloroform fraction exhibited GI50, LC50 and total growth inhibition (TGI) of ~22.5, ~68.75, and ~43.75 µg/mL against breast cancer, respectively, where as GI50, and TGI of ~35.4 and ~55.8 µg/mL against lung cancer cells, respectively. However, the aqueous fraction showed no cytotoxicity against both cell lines.
DISCUSSION AND CONCLUSION: These results have justified the ethnomedicinal uses of the plant against tumor-related ailments. Isolation of the constituents responsible for the observed activity needs to be carried out to further support this claim.

INTRODUCTION: Synthesis of novel substituted 5-[morpholino(phenyl)methyl]-thiazolidine-2,4-diones and screening for their in vivo hypoglycaemic activity and in vitro anti-inflammatory activity. Molecular docking studies to find out active potential lead molecules.
METHODS: Substituted aromatic aldehydes, thiazolidine-2,4-dione and morpholine on mannich reaction gives title compounds. Characterized by physical and spectral methods. In vivo hypoglycemic activity was carried out on Alloxan induced Wister albino rats by tail tipping method. In vitro anti-inflammatory activity was performed by Human Red Blood Cell (HRBC) membrane stabilization and protein denaturation methods. Using AutoDock, molecular docking studies were carried out to find out best fit ligands.
RESULTS: Series of substituted 5-[morpholino(phenyl)methyl]-thiazolidine-2,4-diones were synthesized and chemically they were confirmed by spectral techniques. Acute toxic studies of in vivo hypoglycemic activity results revealed that compounds 4c, 4h, and 4n exhibited good activity at 35 mg/kg body weight. Chronic toxic study results indicate that compound 4h and 4n exhibited good activity at 70 mg/kg body weight. Anti-inflammatory activity results indicate highest inhibition was shown by the compounds 4k and 4f at 500 µg/ml in HRBC membrane stabilization method. In protein denaturation, highest inhibition was shown by compound 4k at 500 µg/ml. In molecular docking studies, compounds 4h and 4n exhibited higher binding affinity at PPARγ receptor protein and compound 4k exhibited higher binding affinity at COX-1 and COX-2 actives sites.
DISCUSSION AND CONCLUSION: Microwave irradiation technique produced high yield at low reaction times. Presence of electron releasing group at para position of the phenyl ring may have ability to produce hypoglycaemic activity and presence of electron withdrawing groups at para position of phenyl ring possess anti-inflammatory activity. The results showed that some compounds exhibited good hypoglycaemic and anti-inflammatory activities. Compounds 4h and 4n exhibited higher binding affinity at PPARγ receptor protein and compound 4k exhibited higher binding affinity at COX isoenzymes active sites in molecular docking studies.

INTRODUCTION: The forced degradation determine the intrinsic stability of the molecule by establishing degradation pathways in order to identify the likely degradation products. The objective of present research work was to establish intrinsic stability and forced degradation profiling of olopatadine hydrochloride.
METHODS: The intrinsic stability of olopatadine hydrochloride has been evaluated by RP-HPLC method, where the mixture of 0.1% formic acid and organic phase (methanol: acetonitrile; 50: 50 % v/v) was used as mobile phase at 1.0 mL/min in gradient mode. Different stress conditions have been employed to explore the intrinsic stability of olopatadine hydrochloride.
RESULTS: In acidic condition, five degradation products (DPs) viz. OLO1, OLO2, OLO3, OLO4 and OLO5 were observed. OLO5 was major DP which was increased with time and peak area of OLO was decreased. In addition to OLO3 and OLO5; two more DPs were observed in alkaline condition viz. OLO6, and OLO7 in alkaline condition. OLO5 and OLO6 were two major DPs; OLO5 was increased with time while OLO6 has zig-zag pattern of peak area with time. All DPs of neutral condition were also found in acidic condition while OLO3 and OLO5 were common in all three type of hydrolytic degradation.
DISCUSSION AND CONCLUSION: Thus, OLO has similar pattern of degradation profiling in all hydrolytic conditions (acidic, alkaline and neutral). No degradation was found in thermal, UV light and oxidative conditions for ten days. OLO-Imp was recognized as analogue structure of OLO and proposed as 11 - [(3-dimethylamino)- propylidene] - 6, 11-dihydro-dibenz[b,e]oxepin-2-propanoic acid in standard drug. OLO1 was identified as (2-(4-(dimethylamino)butyl) phenyl)methanol which may be formed by cleavage of tricyclic ring in neutral condition.

GİRİŞ ve AMAÇ: Bu çalışmada, F. carica yapraklarına ait su ve metanol ekstrelerinin diyabet ve Alzheimer hastalığı ile ilişkili enzimlerin inhibisyonu üzerine etkisinin araştırılması amaçlanmıştır. Ayrıca, ekstrelere ait biyoaktif bileşenler, antikanser, antioksidan ve antimikrobiyal etkiler de araştırılmıştır.
YÖNTEM ve GEREÇLER: Ekstrelerdeki biyoaktif bileşikler gaz kromatografisi-kütle spektrometresi (GC-MS) metodu ile belirlenmiştir. Antioksidan aktivite, DPPH, ABTS radikal süpürücü, toplam fenol ve flavonoid içeriği, ferrik indirgeme gücü ve demir şelasyon yöntemleriyle değerlendirilmiştir. Antikanser, antikolinesteraz ve antimikrobiyal etkinlikler ise sırasıyla XTT yöntemi, Ellman yöntemi ve mikrodilüsyon tekniği yöntemi ile belirlenmiştir.
BULGULAR: Elde ettiğimiz sonuçlar su ve metanol ekstreleri arasında kimyasal bileşim açısından farklılık olduğunu ve her iki ekstrenin de güçlü antioksidan aktiviteye sahip olduğunu göstermiştir. Benzer şekilde, her iki ekstrede güçlü α-glikozidaz ve α-amilaz aktivite gösterirken, su ekstresi metanole göre daha güçlü asetilkolinesteraz ve butirilkolinesteraz inhibisyon etkiye sahiptir. F. carica metanol ekstresi MDA-MB-231 hücreleri üzerinde güçlü antikanser etki, Escherichia coli ve Staphylococcus aureus’e karşı ise orta düzeyde antimikrobiyal etki göstermiştir.
TARTIŞMA ve SONUÇ: Bulgularımız, F. carica yapraklarının kanser, diyabet ve Alzheimer hastalığında umut verici bir terapötik ajan geliştirmek için değerli bir kaynak olabileceğini düşündürmektedir.

INTRODUCTION: The present study was aimed to investigate the inhibitory activities of enzymes, related with diabetes mellitus and Alzheimer’s disease of the methanol and water extracts of F. carica leaves extracts. The bioactive compounds, anticancer, antioxidant, and antimicrobial effects of the extracts were also investigated.
METHODS: The bioactive compounds in the extracts were determined by gas chromatography-mass spectrometry (GC-MS) method. The antioxidant activity was evaluated by DPPH, ABTS radical scavenging, total phenol and flavonoid content, ferric reducing power and iron chelating method. The anticancer, anticholinesterase, and antimicrobial effects were investigated using the XTT assay, Ellman method, and microdilution technique, respectively.
RESULTS: Our results showed that between the water and methanol extracts there was a difference in terms of chemical composition. The antioxidant results suggested that both extracts have strong antioxidant activity. Similarly, both extracts showed strong α-glucosidase and α-amylase inhibition activity, while the water extract has higher inhibition activity than the methanol extract against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The methanol extract of F. carica exhibited significant anticancer activity on MDA-MB-231 cells and showed moderate antimicrobial activities against Escherichia coli and Staphylococcus aureus.
DISCUSSION AND CONCLUSION: Our results suggest that F. carica leaves could be a valuable source for developing a promising therapeutic agent in cancer, diabetes, and Alzheimer’s disease.

INTRODUCTION: Simple, specific, accurate, precise, sensitive and cost effective spectrophotometric methods have been developed and validated for quantification of Lornoxicam (LOR) and Mesalamine (MES) drugs in pure form and in pharmaceutical formulations.
METHODS: Shimadzu Double – beam UV – Visible Spectrophotometer 1800 having spectral bandwidth of 0.1 nm with wavelength accuracy ±0.1 nm and a pair of 1 cm path length matched quartz cells were used to measure absorbance of the resulting solution.Method (I) is used for the quantification of LOR which is based on the measurement of absorbance of bluish green coloured chromogen complex at 760 nm which is formed by reaction of LOR with ferric chloride and potassium ferricyanide (redox technique). Method (II) is used for the quantification of MES that is based on measurement of absorbance of yellow coloured chromogen at 400 nm which is formed by the condensation reaction of the primary amino group of MES with salicylaldehyde reagent (SA) (Schiff base formation).
RESULTS: Both the methods obeyed Beer’s law in concentration range of 0.5-4.5 μg/mLand 0.2-1.7 μg/mL with good correlation coefficients of 0.9974 and 0.998 for Methods (I) and (II) respectively.
DISCUSSION AND CONCLUSION: The developed method is simple, sensitive, specific which is validated statistically as per ICH guidelines and can be used in routine analysis of LOR and MES pharmaceutical dosage forms.

INTRODUCTION: Sepsis is a clinical illness with the high rate of mortality in all over the world. Oxidative stress considered as the main phenomenon which occurs in sepsis. Rosa Damascena supposed as an ancient herbal planet with high pharmacological activities.
METHODS: CLP operation as a standard model was done to induce sepsis in rats. Male adult rats were randomly divided into 5 groups. Rosa Damascena E.Os (50 and 100 mg/kg.bw), was gavaged orally for 14 days, and in the day 15th, CLP was performed. After 24 hours, the blood samples and liver tissues were removed in order to measure oxidative stress (MPO, MDA, GSH, GST, FRAP) and biochemical parameters (ALP, AST, ALP, bilirubin) together with plasma PGE2 and COX-2 expression.
RESULTS: We deduced that E.Os had capable to modulate all of the oxidative stress, antioxidant and anti-inflammatory parameters induced by CLP as characterized by the elevations in MPO and MDA levels as well as increases in AST and ALT concentrations concomitant with PGE2 and COX-2 increments. The antioxidant defense system such as GSH and FRAP was also increased in E.O treated groups.
DISCUSSION AND CONCLUSION: Our results showed that E.Os has antioxidative and hepatoprotective activities through reducing the oxidative injury in sepsis caused by CLP.

INTRODUCTION: Azithromycin dihydrate is a macrolide antibiotic used for the treatment of several types of bacterial infections. The drug shows low oral bioavailability due to its low solubility. In this present work solid lipid nanoparticles of azithromycin dihydrate has been formulated, keeping in view to enhance the solubility and rate of dissolution of the drug.
METHODS: The azithromycin dihydrate loaded stearic acid nanoparticles were formulated by high shear homogenization method using three different surfactants namely Tween 20, Poloxamer 188 and Poloxamer 407 at a varied lipid surfactant ratio while keeping the quantities of active ingredient constant. Twelve such formulations were prepared. The nanoparticles obtained were evaluated for drug content, % drug loading, % entrapment efficiency, particle size analysis, zeta potential, surface morphology, Fourier Transmission infrared spectroscopy, invitro drug release,stability study.
RESULTS: All the formulations showed good entrapment efficiency and high percentage of invitro release with a particle size suitable for lymphatic absorption. The nanoparticles formulated with poloxamer 188 showed better characteristics compared to other surfactants.
DISCUSSION AND CONCLUSION: This study indicates that stearic acid nanoparticles of azithromycin dihydrate prepared by high shear homogenization method can be successively used for improvement of dissolution and thereby oral bioavailability of the drug.

GİRİŞ ve AMAÇ: Bu çalışma, 1-(4-((2-(4-sübstitüefenil)hidrazono)metil)fenil)-1H-1,2,4-triazol türevlerinin sentezlerini yaparak yapılarını aydınlatmayı ve antimikobakteriyel aktivitelerini incelemeyi amaçlamaktadır.
YÖNTEM ve GEREÇLER: Bu çalışmada hedef bileşikler (2a-h), 4-(1H-1,2,4-triazol-l-il)benzaldehidin uygun fenilhidrazinlerle kondenzasyonu ile elde edilmiştir. Bileşiklerin yapıları, IR, 1H-NMR ve kütle spektrometrisi ile aydınlatılmıştır. Antimikobakteriyel aktiviteleri, M. tuberculosis H37Rv'ye karşı in vitro olarak incelenmiştir.
BULGULAR: Aktivite sonuçları incelendiğinde, metilsülfonil sübstitüe türevin 2f serinin en aktif üyesi olduğu bulunmuştur.
TARTIŞMA ve SONUÇ: Metilsulfonil sübstitüe türevin dikkate değer antimikobakteriyel aktivite göstermesine rağmen, sentezlenen bileşiklerin hiçbirinin M. tuberculosis’e karşı izoniazit, rifampin, etambutol ve siprofloksazin kadar etkili olmadıkları bulunmuştur.

INTRODUCTION: The aim of this study is to synthesize, characterize and screen some new 1-(4-((2-(4-substitutedphenyl)hydrazono)methyl)phenyl)-1H-1,2,4-triazole derivatives for their antimycobacterial activities.
METHODS: The target compounds (2a-h) were gained by condensation of 4-(1H-1,2,4-triazol-1-yl)benzaldehyde with appropriate phenylhydrazines. Their structures were elucidated by IR, 1H-NMR and mass spectrometry. The antimycobacterial activities of the compounds were determined in vitro against M. tuberculosis H37Rv.
RESULTS: The biological assay results showed that the methylsulfonyl substituted derivative 2f displayed the highest antimycobacterial activity in this series.
DISCUSSION AND CONCLUSION: Although the methylsulfonyl substituted derivative exhibited significant antimycobacterial activity, none of the synthesized compounds was found as effective as isoniazid, rifampin, ethambutol and ciprofloxazin against M. tuberculosis.

INTRODUCTION: Vitex grandifolia belongs to Lamiaceae or Labiatae family, it consists of flowering plants and it is also called mint-family and the Yoruba people of South-West in Nigeria called it “Oriri or Efo oriri”. This plant is classified as one of underutilized vegetable, little is known about its phytochemistry and its biological evaluations.
METHODS: The methanol extracts of the dried leaves and stem of the plant was subjected to fractionation and isolation using vacuum layer and column chromatography methods. The structures of the compounds were elucidated using spectroscopic techniques including IR, 1D and 2D-NMR and by comparison with the data reported in the literature. They were evaluated in vitro for the inhibition of monoamine recombinant human MAO-A & B and anti-inflammatory activities.
RESULTS: Three known flavonoids were isolated from its methanolic part of the leaves of Vitex grandifolia for the first time to the best our knowledge i.e. isoorientin (1), orientin (2) and isovitexin (3). Most of the isolated compounds showed selective inhibition of monoamine oxidase B, inhibition of MAO B by Isoorietin (1) and orientin (2) were 9-fold more potent (IC50 (μg/mL) of 11.08 and 11.04) compared to the inhibition of MAO A (IC50 (μg/mL) of ˃100) while clorgyline and deprenyl were used as positive standards. The isolated flavonoids displayed good activity against NF-Kb assay with IC50 (μg/mL) of 8.9, 12 and 18. The study establishes the link between the structure and the biological activities on the basis of the different patterns of substitution particularly C2=C3 double bond and position of glucose moiety.
DISCUSSION AND CONCLUSION: This study is the first to establish the phytochemistry of the polar part of Vitex grandifolia, the anti-inflammatory and neurodegenerative protective role of these isolated compounds.

GİRİŞ ve AMAÇ: Pseudomonas aeruginosa, antibiyotiklere oldukça dirençli ve biyofilm oluşturma yeteneği nedeniyle hayatı tehdit eden enfeksiyonlara neden olabilmektedir. Antimikrobiyal peptidlerin aktivitelerini taklit eden cerageninler, P. aeruginosa’ya karşı da güçlü etki gösteren yeni umut verici ajanlardır. Çalışmamızın amacı, cerageninlerin P. aeruginosa suşlarına karşı antibakteriyel ve antibiyofilm aktivitelerini değerlendirerek, kolistin ve siprofloksasinle karşılaştırmaktır.
YÖNTEM ve GEREÇLER: 25 P. aeruginosa suşunun biyofilm oluşturma özellikleri ve CSA-13, CSA-44, CSA-131, CSA-138, siprofloksasin ve kolistine karşı duyarlılıkları araştırılmış ve antimikrobiyal ajanların MİK değerleri belirlenmiştir. Biyofilm çalışmaları için kuvvetli biyofilm oluşturan dört suş seçilerek, antimikrobiyal ajanların sesil MİK değerleri, ve adezyon ve biyofilm oluşumuna etkileri araştırılmıştır.
BULGULAR: CSA-13, CSA-44, CSA-131, CSA-138, siprofloksasin ve kolistinin MİK50 (µg / ml) değerleri sırasıyla 8, 8, 8, 16, 1 ve 2, olarak bulunmuştur. Sesil MİK değerlerinin ise planktonik MİK değerlerinden daha büyük olduğu bulunmuştur. CSA-13, CSA-44 ve CSA-131’in, 4 saatlik inkübasyondan sonra, CSA-138, siprofloksasin ve kolistinin ise 1 saatlik inkübasyondan sonra biyofilme karşı daha etkili oldukları tespit edilmiştir. Adezyon inhibisyonu için kolistinin (% 45'e kadar inhibisyon), biyofilm oluşumu inhibisyonu için ise yine kolistin, CSA-131 ve CSA-138’in (% 90'a kadar inhibisyon) en etkili ajanlar oldukları tespit edilmiştir.
TARTIŞMA ve SONUÇ: Çalışmamızda CSA-131 ve CSA-138'ün P. aeruginosa'nın biyofilmlerine karşı konvansiyonel antibiyotiklere alternatif olarak kullanılabileceği vurgulanmıştır.

INTRODUCTION: Pseudomonas aeruginosa can cause life-threatening infections that are difficult to treat due to its high resistance to antibiotics and to the ability to form antibiotic tolerant biofilms. Ceragenins, designed to mimic the activities of antimicrobial peptides, represent a promising new group of antibacterial agents that display potent anti-P. aeruginosa activity. The aim of this study was to evaluate the antibacterial and antibiofilm activities of the ceragenins in comparison to colistin and ciprofloxacin against P. aeruginosa strains.
METHODS: Biofilm formation and determination of MIC values of ceragenins, CSA-13, CSA-44, CSA-131, CSA-138, ciprofloxacin and colistin were evaluated against 25 P. aeruginosa isolates. Four good biofilm-producing strains were chosen for biofilm studies, and sessile MICs and inhibition of adhesion and biofilm formation were evaluated.
RESULTS: MIC50 (µg/ml) values of CSA-13, CSA-44, CSA-131, CSA-138, ciprofloxacin and colistin were 8, 8, 8, 16, 1 and 2, respectively. The SMICs for molecules were found greater than planktonicMICs. CSA-13, CSA-44 and CSA-131 were found to be more efficient after 4 hour incubation although CSA-138, ciprofloxacin and colistin after 1 hour incubation. The most efficient agent for inhibition of adhesion was found colistin (up to 45%). CSA-131, CSA-138 and colistin were found the most efficient agents for inhibition of biofilm formation (up to 90%).
DISCUSSION AND CONCLUSION: Our study highlights the potential of CSA-131 and CSA-138 as potential alternative agents to conventional antibiotics for the eradication of biofilms of P. aeruginosa.

GİRİŞ ve AMAÇ: Poli (p-aminobenzen sülfonik asit) modifiye sensörün karbon elektrotlar kullanılarak metil dopa (MD) ve askorbik asitin duyarlı ve güvenilir şekilde tespit edilmesi
YÖNTEM ve GEREÇLER: Elektropolimerizasyon, 0.1 M KCl çözeltisi içerisinde çevrimli voltametri (CV) ile gerçekleştirildi. Modifiye sensör, 2-12 pH aralığında diferansiyel pulse voltametri (DPV) teknikleri ile ortaya çıkan metil dopanın oksidasyonu için yüksek elektrokatalitik etkiye sahiptir.
BULGULAR: MD'nin voltametrik tayini için, en iyi sonuçlar fosfat tampon çözeltisi (PBS) (pH 3) DPV tekniği ile elde edildi. MD için konsantrasyon aralığı, DPV ile 3.2 x 10-8 ila 4.7 x 10-7 M arasındaydı. Duyarlılık çalışmalarında, kantifikasyon sınırı (LOQ) ve tespit limiti (LOD) sırasıyla 10.6 nM ve 5.0 nM idi. Değiştirilen sensör, bazı gerçek numunelerde eş zamanlı olarak askorbik asit (AA) gibi MD ve parazitlerin belirlenmesi için kullanılmıştır. Elde edilen sonuçlar, modifiye edilmiş elektrot ve önerilen yöntemin iyi duyarlılık, tekrarlanabilirlik, tekrarlanabilirlik ve stabiliteye sahip olduğunu ortaya çıkardı.
TARTIŞMA ve SONUÇ: Elde edilen sonuçlar, modifiye edilmiş elektrot ve önerilen yöntemin iyi duyarlılık, tekrarlanabilirlik, tekrarlanabilirlik ve stabiliteye sahip olduğunu ortaya çıkardı.

INTRODUCTION: Methyldopa, is a catecholamine which is known by its chemical name 2-Methyl-3-(3,4-dihydroxyphenyl)-DL-alanine (Figure 1), and it is widely used to lower blood pressure. MD is a centrally acting adrenal-receptor that reduces high blood pressure and sympathetic tone.1 In adrenergic nerve terminals, it is converted to α-methyl noradrenaline, and its antihypertensive effect seems to be owing to this agent stimulate the central adrenoreceptors.2


Figure 1. Molecular structure of methyldopa.

In general, high-performance liquid chromatography with UV detection3, polarographic4, potentiometry5 and ultra viole visible spectrophotometry.6 Quantitative analysis of various catecholamine moleculas was performed electrochemically by flow injection technique.7,8 However, many of these techniques are require expensive equipment and time consuming. In addition, since this catecholamins are electrochemically active, it is also possible to determine the nature of the molecules that provide neurotransmission by electrochemical methods. Therefore, it is important to detection of MD in the presence of AA by a reliable method which has good selectivity and sensitivity.

Ascorbic acid (vitamin C) is a biologically and industrially important substance. Especially in food and pharmacological industries, it is very important to analyze this substance which is mostly used in the shortest time and with the most sensitive techniques).9 The coexistence of ascorbic acid, MD and other catecholamines with very close oxidation potentials leads to the response obtained by electrochemical techniques. For this reason, the increased sensitivity and selectivity of the new sensors produced to the MD has long been the subject of researchers working on. Using the polymer modified electrodes solve this problem. Electrochemical behavior of MD was studied at various polypyrrole electrodes.10-14

However, some disadvantages exist in the previously reported modified electrodes. AA is present as an anion in physiological pH (7.4), whereas MD is present as a cation. There are high electron density sulfo groups and electron-rich N atoms in the structure of p-(ABSA). For this reason, a negatively charged polymer film is required to eliminate the interference of AA in the determination of MD. The p-aminobenzene sulfonic acid molecule has a high electron density sulfo groups, and p-(ABSA) films are negatively charged. Due to the electrostatic repulsion between the negatively charged sulfo groups and the ascorbic acid anions in the modified sensor, the ascorbic acid shifts to a more negative potential and the dopaminic acid can be easily separated from the ascorbic acid. The p-(ABSA) modified sensor can show high selectivity against MD.15
In this study, electroanalytical methods were developed to detect methyl dopa in drug samples rapidly, reliably and sensitively using electrode modified with poly (p-ABSA). It has been determined that the modified sensor can be utilized to the MD determination even in the presence of ascorbic acid at the same time.

The analytical determination parameters such as the LOD, the quantitative determination LOQ and the concentration range were determined, and the amount of MD in the drug tablets and blood serum was found. To test the accuracy of the applied voltammetric method, MD recovery studies were performed in real samples.

METHODS: Materials
All chemicals were of analytical purity and were procured from Merck (Darmstadt, Germany) or Sigma Chemical Company. Prior to the polymerization, the solutions of monomer were held in the nitrogen gas atmosphere for about 10 minutes, and during the electropolymerization, the environment was covered with nitrogen gas. Voltammetric experiments were carried out in the phosphate buffer solution (pH 3.0). Methyl dopa and AA solutions were freshly prepared before the experiments. All solutions were made up with ultra-pure water.

Instrumentation
In voltammetry experiments, BAS (Bioanalytical Systems, Inc.) 100BW electrochemical analyzer was used. This analyzer is connected to a personal computer and the device is controlled, data stored and processed by means of software loaded and running under MS-Windows. This electrode system consisting of an Ag/AgCl reference electrode (CHI), a glassy carbon disc working electrode (geometric area: 6.85 mm2, CHI) and a Pt wire coil auxiliary electrode (CHI) was used.
Modification of Poly (p-ABSA) Sensor
Before modification, the working glassy carbon electrode (GCE) was cleared up using 0.3 and 0.05 µm Al2O3 slurry on polishing materials. After polished GCE was sonicated in 1: 1 nitric acid solution for 10 min and washed with ultra-pure water. Afterward, GCE was electrochemically cleaned by 20-times cycling in the potential range of −0.7 to 1.7 V with a scan rate of 100 mV/s in 0.5 M H2SO4. After that, the electrode was plunged into 0.1 M KCl solution containing 5.0 mM p-ABSA and modification procedure was performed by cyclic sweeping from -1.5 to 2.5 V for 14 cycles at 50 mV/s. Then, the modified sensor was conditioned by cyclic voltammetry in the potential range of -0.5-0.5 V with 100 mV/s in pH 3.0 PBS and was stored in PBS (pH 3.0).

RESULTS: Electropolymerization of p-Aminobenzene Sulfonic Acid
Figure 2 shows that the electropolymerization of p-ABSA at the GCE surface. the electropolymerization was performed in 0.1 M KCl solution containing 5.0 mM p-ABSA at a GCE by cyclic voltammetry technique in the potential range of -1.5-2.5 V. In the first cycle, two reduction peaks were obtained at 0.452 V (peak A) and 0.449 V (peak B), which might be related to the reduction of p-ABSA. Again in the first cycle, an oxidation peak observed at 0.824V (peak C). In the next and subsequent cycles, following the continuous scan, broader peaks were monitored that proved that the polymer film was constantly growing. It could be observed that the film growth was faster for the first five cycles than for the other cycles and also, the next cycles are no longer stable. From these, it could be said that p-ABSA was coated on the GCE surface by electrodeposition. A brown polymer was formed that was properly bonded on the GCE surface.



Figure 2. CVs of 5 mM p-aminobenzene sulfonic acid in 0,1 M KCl at GCE, Scan rate: 50 mV/s, 14 cycle.

The Effect of Film Thickness on MD Response
The film thickness, which is the number of cycles of electropolymerization, is one of the most important factors determining the polymer film selectivity property. By altering the amount of charge consumed during electropolymerization, it is possible to obtain poly (p-ABSA) films at desired thicknesses. Different film thicknesses were obtained by varying the cycles of the cyclic voltammetry parameter. The selectivity characteristics of poly (p-ABSA) sensors prepared in the range of 6–20 cycles to MD and AA were systematically examined. From the DPV results of MD, it was observed that the regular and repetitive responses could be obtained at 14 cycles film.
Electrochemical behavior of MD at poly(p-ABSA) modified sensor
The voltamograms achieved by the cyclic voltammetry technique of MD show a reduction potential of ~ 200 mV potential and an oxidation peak of ~ 220 mV potential (Figure 3). As seen from the cyclic voltamograms, the anodic and cathodic peak currents differ from each other, indicating that the MD molecule exhibits a semi-reversible reaction.


Figure 3. CVs of 0.01 mM MD in 0.1 mM PBS (pH 3.0) (A) GCE (B) at poly(p-ABSA) modified sensor. Scan rate: 50 mV/s.

Electrolyte Type Effect on Voltammetric Behavior of Methyl Dopa

By selecting an appropriate support electrolyte solution, it creates a conductive environment between the submerged electrodes. Apart from this basic purpose, the support electrolyte is doped in the polymer coming into the solution.


Figure 4. Electrolyte effect on voltammetric analysis of 0.01 mM Methyl Dopa on poly (p-ABSA) sensor. A) PBS (pH 7,0), B) NaClO4 C) KCl, D) NaCl, E) NaNO3 and F) Na2SO4.

The choice of support electrolyte depends on its resolution, dissociation degree and nucleophilic character. For this purpose, voltammograms of MD in Na2SO4, PBS (pH 7,0), NaNO3, NaClO4, NaCl and KCl electrolytes were taken (Figure 4). While taking a voltamogram at pH 7.0 in PBS, voltamograms were taken at the native pH of the other electrolyte species.

pH effect on the peak potential and current of MD
To observe how methyl dopa behaves in relation to pH in PBS, the potential-current relationships at pH 2-11 are plotted. Besides, Figure 5 indicates the relation of maximum peak potential and current on pH of electrolyte. As the pH increases for methyl dopa, the peak potentials are shifted to lower potentials.


Figure 5. pH effect on (A) current and (B) potential of 0.01 mM methyl dopa using DPV technique. Scan rate, 50 mVs-1


Determination of MD in the presence of AscorbicAcid
Determination of MD in poly (p-ABSA) was done with differential pulse voltammetry. Differential pulse voltamograms of different concentrations of MD on poly (p-ABSA) are shown in Figure 6. The results obtained showed that the anodic peak currents of MD were linear at a concentration range of 1 μM to 300 μM. The calibration equation for MD is calculated as Ipa (μA) = 0,56x + 48,42 C (μM). Calibration chart was drawn in the concentration range of 3.2 x 10-8 - 4.7 x 10-7 M using DPV technique. LOD and LOQ were detected as 5.0x10-9 nM and 10.6 nM (S/N=3), respectively.


Figure 6. A) Differential pulse voltammograms and B) calibration graphs in increasing concentration of MD at poly (p-ABSA) modified sensor. MD concentrations (μM) were in the range of 0,0 - 300,0 in 0.1 M PBS (pH 3.0).

Figure 6A shows the peak of increasing concentrations of MD in the presence of 0.5 mM constant ascorbic acid. MD concentrations were 0,0, 1.0, 8.0, 10.0, 20.0, 30.0, 40.0, 50.0, 75.0, 100.0, 125.0, 150.0, 200.0, 250,0 and 300,0 μM. As can be seen, the ascorbic acid peaks remain the same while the methyl dopa peaks increase proportionately. The fact that methyl dopamine gives this result in the presence of ascorbic acid at pH 3.0 reveals that methyl dopa can be determined by this method in real samples, for example in samples taken from human beings or animals.

Figure 7. The increasing concentration of MD (0.01, 0.015, 0.020, 0.025, 0.030, 0.035 mM) with 0.5 mM ascorbic acid at poly (p-ABSA) modified sensor in 0.1 M PBS (pH 3.0).

In Figure 7, peak currents of ascorbic acid in increasing concentrations are observed in the voltammogram, as well as MDs with a constant concentration of 0.01 mM in Figure 8. The higher the ascorbic acid concentration is increased, the more the MD peaks are not deviated. This suggests that the method can be applied even in samples containing high concentrations of ascorbic acid.

Figure 8. The increasing concentration of ascorbic acid (0.1, 0.2, 0.3, 0.4, 0.5, 0.6 mM) beside 0.01 mM methyl dopa at poly (p-ABSA) in 0.1 M PBS (pH 3.0).

Analytical applications
Five Alfamet tablets containing 250 mg MD in each tablet were directly weighed and powdered into the mortar. The amount of the calculated amount corresponding to the 100 mM concentration stock solution was weighed and transferred to a 10 mL volumetric flask and the volume was supplemented with ultra-pure water. The contents of the flask were subjected to centrifugation at 5000 rpm for 15 minutes to effect complete dissolution. Insoluble auxiliary substances dissolved. After then, the clear solution was taken up in the appropriate amount and the water was diluted to deionized water. The amount of MD in MD tablets was calculated with reference to the appropriate calibration graphs. Furthermore, the proposed techniques were tested by performing recovery tests. The obtained results are given in Tables 1 and 2. The proposed techniques can be successfully applied to MD analysis on tablets without any interference.

The quantity of MD in the tablets was computed from the suitable calibration charts. Furthermore, the validity of the proposed techniques was checked by carrying out recovery studies. Recovery results and the results obtained from the calibration chart can be seen in Tables 1 and 2. The proposed method was successfully performed to real samples beside interferences.

Table 1. Application of poly (p-ABSA) sensor to Methyl Dopa
Parameters Slope, mA/µM Intercept, µA Correlation coefficient, r
Proposed method 0.56 48.42 0.982

Table 2. Detection of MD in commercial tablets
Parameters Labeled, mM Found, mM RSD*, % Recovery, %
Proposed method 1 0.979 0.14 97.9
Blood Serum 1 0.764 0.22 76.4
* RSD: relative standard deviation.


DISCUSSION AND CONCLUSION: The results show that the proposed method can be easily used in the determination of catecholamines in drug samples and clinical analyzes. It has been observed that this method may be used to identify catecholamines in the blood serum.

INTRODUCTION: Leflunomide (LFNM) is a drug belongs to isoxazole derivative and having immunosuppressive and anti-inflammatory activities. Literature search confirms that there is no method reported for the simultaneous estimation of LFNM and its related impurities A and B in pharmaceutical dosage forms and in bulk drug. Hence the present work aimed to develop a simple stability indicating RP-HPLC method for the separation and quantification of LFNM and its impurities A and B.
METHODS: Systematic trails of method condition like mobile phase ratio, pH, flow rate, stationary phase and detector wavelength was performed for the simultaneous analysis of LFNM and its related impurities A and B. The developed method was validated as per the ICH guidelines including forced degradation studies
RESULTS: Optimized separation was achieved on Thermo Scientific Hypersil ODS C18 column (250mm×4.6mm; 5µ id) using mobile phase composition of acetonitrile, methanol and 0.1M sodium perchlorate in the ratio of 40: 30: 30 (v/v); pH 4.6, at a flow rate of 1.0mL/min in isocratic elution. UV detection was carried at wavelength of 246nm. Well resolved peaks were observed with high number of theoretical plates, less tailing factor and reproducible relative retention time and response factor. The method was validated and all the validation parameters were found to be within the acceptance limit. Stability tests were done through exposure of the analyte solution to five different stress conditions i.e 1 N HCl, 1 N NaOH, 3% H2O2, thermal degradation of powder and exposure to UV radiation. The method can successfully separate the degradation products along with both the impurities studied. The % degradation was also found to be less.
DISCUSSION AND CONCLUSION: The method developed for LFNM is simple, precise and can applicable for the separation and quantification of LFNM and its related impurities in bulk drug and pharmaceutical formulations.

INTRODUCTION: The present study was conducted to identify the phytoconstituents present in different extracts of Sargassum wightii and to assess the toxicity of its ethanol extract.


METHODS: Successive solvent extraction and total ethanol extraction of Sargassum wightii were performed and preliminary phytochemical screening was carried out. Acute toxicity study of ethanol extract of Sargassum wightii (ESW) was carried out. Subchronic toxicity study of ESW was carried out with the doses of 100, 200, 400 mg/kg. The animals were observed for changes in body weight, food and water intake. At the end of study, relative weight of vital organs were noted followed by histopathological examinations. Various hematological, biochemical estimations were also carried out.

RESULTS: Phytochemical screening of Sargassum wightii revealed the presence of alkaloids, carbohydrates, glycosides, phenolic compounds and tannins. ESW did not induce any mortality or pre-terminal death in the acute toxicity study. There were no significant difference in body weight, relative weight of vital organs (except brain), food and water intake compared to the control group. Histopathological examination showed normal architecture suggesting absence of pathological lesions. Hematological and biochemical parameters were also found to be comparable to the control group except reduction in glucose and cholesterol level which is postulated to be beneficial.
DISCUSSION AND CONCLUSION: Presence of various phytoconstituents in Sargassum wightii is evident that it could be a potential source for treating different ailments. No significant toxic effects were observed with the treatment of ESW. Thus, it is proposed to be safe and can be recommended for long term treatment.

GİRİŞ ve AMAÇ: Endemik Ferula tenuissima köklerinin fitokimyasal yönden incelenmesi ve elde edilen saf bileşiklerin PC-3 üzerinde sitotoksik etkilerinin belirlenmesidir.
YÖNTEM ve GEREÇLER: F. tenuissima’ nın açık havada kurutulmuş ve toz haline getirilmiş kökleri (1 kg, 24 saat boyunca 30°C' de sonikasyonda n-hekzan, kloroform (CHCl3) ve metanol (MeOH) (3x2 L, her biri) ile sırasıyla ekstre edildi. Ekstraklar daha sonra süzüldü. Sıvı ekstreler, vakum altında kuruluğa kadar uçuruldu. Kromatografik yöntemler ile bileşikler elde edildi ve bileşiklerin yapıları spektral yöntemler ile belirlendi (1D-, 2D NMR and LC-MS). Bileşiklerin PC-3 üzerindeki sitotoksik aktiviteleri WST yöntemi ile test edildi.
BULGULAR: Endemik F. tenuissima' nın kurutulmuş köklerinin fitokimyasal incelemesi yapıldı ve üç seskiterpen esteri izole edildi. Teferidin, ferutinin ve elaeochytrin-A daukan tip seskiterpen esterleri olarak belirlendi. Biyoaktivite çalışmasında, Ferutinin en yüksek sitotoksik aktiviteyi IC50: 19.7 µM ile gösterdi.
TARTIŞMA ve SONUÇ: Sonuçlar Ferula tenuissima köklerinin ana bileşiklerinin daukan seskiterpenler ve ferutininin PC-3 hücreleri üzerinde potansiyel bir etkiye sahip olduğunu göstermektedir.

INTRODUCTION: Phytochemical study of endemic Ferula tenuissima roots and determination of the cytotoxic activity of pure compounds obtained on PC-3.
METHODS: Air-dried and powdered roots of F. tenuissima (1 kg) were extracted respectively with n-hexane, chloroform (CHCl3) and methanol (MeOH) (3x2 L, each) by sonication at 30 ºC, for 24h. The extracts were then filtered. The solvents separately evaporated under reduced pressure to dryness. Compounds were isolated by chromatographic methodes and structures of compounds were determined by spectral methodes (1D-, 2D NMR and LC-MS). Compounds were tested for their cytotoxic activities versu PC-3 cell line by WST assay.
RESULTS: Phytochemical investigation of dried roots of endemic F. tenuissima performed and three sesquiterpene esters were isolated. As teferidin, ferutinin and elaocyhtrin-A; daucane-type sesquiterpenes were identified. In the bioactivity study, Ferutinin exhibitited the highest cytotoxic activity with 19.7 µM IC50 value.
DISCUSSION AND CONCLUSION: The results indicate that the main compounds of Ferula tenuissima roots are daucane sesquiterpenes and ferrutinin has potential effect on PC-3 cells.

Geçtiğimiz yıllarda, nanotaşıyıcılar güvenli ve verimli ilaç dağıtımı ve salımı için ideal bir çözüm haline geldi. Bu, temel olarak nanomalzemelerin daha büyük ölçekli formlarıyla karşılaştırıldığında sergiledikleri olağanüstü özelliklerden kaynaklanmaktadır. Bu taşıyıcıların çeşitliliği yüksek biyouyumluluk nedeniyle daha popüler olup, özellikle kanser tedavilerinde daha fazla etkinlik sağlar. Son elli yıl boyunca, nanokristal, lipozomal ve misel tasarımları bu malzemelerin ilaç dağıtımı ve salınımı için çok araştırılmıştır. Başarılı uygulamalar sadece terapötik gelişimde daha fazla odaklanma sağlamakla kalmadı, aynı zamanda farmasötik pazarda da mevcut yeni bir çözüm yarattı. Bu çalışmada, nanotaşıyıcılar araştırmaların kısa bir derlemesi ve ilaç tedavisi için ilaçların üstün yararlarını elde etmek için nanohidrojel, kitosan, grafen/grafen oksit ve katı lipid nanoparçacık tasarımları sunulmuştur. Bu malzemeler biyouymululuğu yüksek ve manipülasyonu kolay olmaları sebebi ile son yıllarda en çok tercih edilen nanotaşıyıcı malzemeleri olmuştur. İlaç dağıtımı ve salınmasında en fazla ilgi çeken bu nanotaşıyıcı malzemeleri, bugüne kadar olan gelişimleri özetlenmiştir. İlaç dağıtımı için nanotaşıyıcı ihtiyacının ve bu nano malzemelerin gelişim sürecinde mevcut durumun daha iyi anlaşılmasıyla, farmasötik teknolojilerinde hastalara daha iyi tedavi sağlama şansı artmaktadır.

Over the past years, nanocarriers have become to be an ideal solution for safe and efficient drug delivery and release. This is mainly due to the extraordinary characteristics that the nanomaterials exhibit when compared with their larger scaled forms. A variety of these carriers are more popular due to high biocompatibility, ensuring greater efficacy especially in cancer treatments. Nanocrystal, liposomal and micelle designs of these materials as nanocarriers for drug delivery and release have been greatly researched throughout the past fifty years. Successful applications have not only ensured a greater focus in therapeutic development but also created a new solution available in the pharmaceutical market. In this study, a brief review of researches focused on nanocarrier materials and designs to achieve superior benefits of drugs for disease treatments is presented. Nanohydrogels, chitosan, graphene oxide and solid lipid nanoparticle nanocarrier designs and applications are selectively given due to the great attraction they have gained from being highly biocompatible and easy-to-manipulate nanocarrier options from organic and inorganic nanocarrier materials. Each summary exhibits the progress that has been achieved up to date. With greater understanding of the current state in the development process of these nanomaterials, there is a rising chance to provide better treatment to patients which is a desperate need in pharmaceutical technologies.