Nesrin Gökhan

6-Benzylidenethiazolo[3,2-b]-1,2,4-triazole-5(6H)-onessubstituted with ibuprofen: synthesis, characterizationand evaluation of anti-inflammatory activity

In this study, the synthesis of 3-[1-(4-(2-methylpropyl)phenyl)ethyl]-1,2,4-triazole-5-thione (2) and its condensed derivatives 6-benzylidenethiazolo[3,2-b]-1,2, 4-triazole-5(6H)-ones (2a-u) are described. The structures of the compounds were elucidated by spectral and elemental analysis. In the pharmacological studies, anti-inflammatory activities of these compounds have been screened. Among the compounds examined, the compounds 2 and 2g possessed the most prominent and consistent activity. In gastric ulceration studies the synthesized compounds were generally found to be safe at a 200 mg/kg dose level.

1-N-Substituted thiocarbamoyl-3-phenyl-5-thienyl-2-pyrazolines : A novel cholinesterase and selective monoamine oxidase B inhibitors for the treatment of Parkinson's and Alzheimer's diseases

Twelve 1-N-substituted thiocarbamoyl-3-phenyl-5-thienyl-2-pyrazoline derivatives were synthesized and their biological interactions with human plasma and erythrocyte acetylcholinesterase (AChE) and butrylcholinesterase (BuChE) enzymes were assessed. Compounds 3i-3l of newly synthesized N-substituted pyrazolines, which were presented as selective and irreversible MAO-B inhibitors in our previous report, were found to inhibit human erythrocyte and plasma AChE activities selectively and non-competitively suggesting that these compounds may interact with a region close to the peripheral site of the enzyme molecule which could shift the proper positioning of the catalytic center. Compounds 3e-3h inhibited both AChE and BuChE activities of human erythrocytes, but the inhibitory potencies of these compounds towards BuChE were found to be higher than that of towards AChE. Inhibition was found to be non-competitive and reversible. These data suggested that newly synthesized N-substituted pyrazoline derivatives can be evaluated as both MAO-B and cholinesterase inhibitors which may have promising features in the treatment of Alzheimers and Parkinsons diseases.

Interaction of rat lung SSAO with the novel 1-N-substituted thiocarbamoyl-3-substituted phenyl-5-(2-pyrolyl)-2-pyrazoline derivatives

SummaryInteractions of twelve new synthesized 1-N-substituted thiocarbamoyl-3-substituted phenyl-5-pyrolyl-2-pyrazoline derivatives with rat lung semicarbazide-sensitive amine oxidase (SSAO) were assessed. Pyrazoline derivatives were synthesized according to previous methods and SSAO was purified from the crude microsomal fractions of rat lung.Three compounds (3e, 3f, 3k) with a p-methoxy group at the phenyl ring inhibited rat lung SSAO non-competitively and irreversibly, and showed higher affinity towards SSAO when expressed in terms of IC50 for SSAO/Monoamine oxidase B (MAO-B). Since these novel pyrazoline derivatives have been found to act as suicide inhibitors of SSAO, the semicarbazide group in these molecules may be responsible for the SSAO inhibitory action. It is suggested that these compounds cannot enter the first small active site cavity of SSAO and may interact tightly with another binding site or with some other reactive groups present in the molecule. Compound 3e showed the highest inhibitory activity on rat lung SSAO. The novel pyrazoline derivatives may be used to discriminate between Cu- and FAD-containing amine oxidases and may have promising features as anti-Parkinson agents if the SSAO-inhibitory effects can be supported by in vivo studies.

Development and Validation of a Capillary Electrophoretic Method for the Determination of Degradation Product in Naphazoline HCl Bulk Drug Substance

Abstract In this study a capillary electrophoretic method is described for the identification and quantitation of the main degradation product napthylacetyletylenediamine (NAED) in naphazoline HCl bulk drug. The effect of temperature, operating voltage, and electrolyte concentration on the resolution was determined by using a multivariate experimental design. The separation was achieved at 15 kV, on a 70 cm (62 cm effective) × 75 μm I.D. capillary at 20°C using 0.1 M, pH 3 phosphate buffer as background electrolyte. The method was validated and satisfactory specificity, linearity, precision, and accuracy results were obtained.

Synthesis of 3-(4-substituted benzoylmethyl)-2-benzoxazolinones and screening antimicrobial activities.

A number of 3-(4-substituted benzoylmethyl)-2-benzoxazolinones have been synthesized by reacting with 2-benzoxazolinone and 4-substituted phenacyl bromide in ethanol. Their chemical structures were confirmed by IR, 1H NMR and elemental analysis. For screening antimicrobial activity, minimum inhibitory concentration (MIC) values were determined against two Gram positive, one Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus) and three yeast-like the fungi (Candida albicans, Candida krusei, Candida parapsilosis).

Analgesic activity of acylated 2-benzoxazolinone derivatives

Ten new benzoxazolinone derivatives having a disubstituted benzoyl group at the six position of the ring were synthesized by reacting 2-benzoxazolinone with aromatic carboxylic acids in the presence of polyphosphoric acid. The structure of the compounds were elucidated by IR, 1H NMR, MS and elemental analysis. Analgesic activity was evaluated by a modified Koster test. Seven compounds showed analgesic activities higher than that of acetylsalicylic acid.

Synthesis of some novel 3-methyl-6-(2-substituted propanoyl/propyl)-2-benzoxazolinone derivatives and anti-nociceptive activity.

In this study, 12 new 3-methyl-6-(2-substituted aminopropanoyl)-2-benzoxazolinone and 3-methyl-6-(1-hydroxy-2-substituted aminopropyl)-2-benzoxazolinone derivatives have been prepared. Their structures have been elucidated by IR, 1H NMR spectra and by elementary analysis. The anti-nociceptive activity of these compounds has been investigated by using a modified Koster test. It was found that most compounds are capable of inducing anti-nociception in animals.

Novel Antiinflammatory Analgesics: 3-(2-/4-Pyridylethyl)-Benzoxazolinone and Oxazolo[4,5-β]pyridin-2-one Derivatives

Twenty‐two new 3‐[2‐(2‐and/or 4‐pyridyl)ethyl]benzoxazolinone and oxazolo[4,5‐b]pyridin‐2‐one derivatives have been synthesized by reacting 2‐and/or 4‐vinylpyridine and appropriate benzoxazolinones and oxazolo[4,5‐b]pyridine‐2‐one. Their chemical structures have been proven by IR, 1H‐NMR, 13C‐NMR, mass spectroscopy, and elemental analysis. The analgesic activities of these compounds were investigated by a modified Koster′s Test. Test results revealed that, at 100 mg/kg dose level, most of the compounds showed significant analgesic activities when compared to aspirin. Therefore the compounds were screened for their antiinflammatory activities using the carrageenan hind paw edema test. Compounds 1, 7, 10, 11, 12, 13, 15, 18, 20, 21 were found more active than indomethacine. In gastric ulceration studies gastrointestinal bleeding was not observed at 100 mg/kg dose level in compounds 1 and 2.

In vivo metabolism of 2-[1′-phenyl-3′-(3-chlorophenyl)-2′-propenylyden]hydraz ino-3-methyl-4(3H)-quinazolinone in rats

SummaryThe aim of this study was to investigate by HPLC the in vivo metabolism of 2-[1′-phenyl-3′-(3-chlorophenyl)-2′-propenylyden]hydrazino-3-methyl-4(3H)-quinazolinone as a substrate, and as a model compound in rats. The substrate was dissolved in DMSO/water (1∶4) and administered intraperitoneally at a dose of 100 mg/kg in a volume of approximately 0.1 mL. Blood samples were taken before and 30 min, 1.5, 3, 6, 9, 11, 30 and 48 h after i.p. drug administration. The chromatographic separation of the substrate and its metabolites was performed using a stainless steel Novopak C18 column (150 × 4.6 mm i.d., 5-μm particle size). The optimal composition of the mobile phase was reached by introducing different mixtures of pure acetonitrile and water in a linear gradient system. Following the biotransformation of this compound, 2-hydrazino-3-methyl-4(3H)-quinazolinone (M1) and 3-(3-chlorophenyl)-1-phenylprop-2-en-1-one (M2) derivatives were identified together with substrate by comparing them to reference standards using HPLC-UV/DAD. In addition, the composition of these metabolites and substrate was confirmed by LC-MS in plasma.

Method validation in pharmaceutical analysis : From a general approach to capillary electrophoresis

This paper gives a rapid review on analytical method validation with special emphasis on capillary electrophoresis. The primary validation parameters such as accuracy, precision, specificity, linearity, and sensitivity are defined; the evaluation procedures are outlined. The recent reports covering the applications on the subject are summarized and discussed.