Some 3-thioxo/alkylthio-1,2,4-triazoles with a substituted thiourea moiety as possible antimycobacterials

A series of novel N-alkyl/aryl-N'-[4-(4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thione-5-yl)phenyl]thioureas 1-19 and three S-alkylated representatives of the former, N-alkyl/aryl-N'-[4-(3-aralkylthio-4-alkyl/aryl-4H-1,2,4-triazole-5-yl)phenyl]thioureas 20-22, were synthesized and tested for antimycobacterial activity against Mycobacterium tuberculosis H37Rv as well as Mycobacterium fortuitum ATCC 6841 which is a rapid growing opportunistic pathogen. Compounds 4 and 9-11 were found to possess the same MIC value with that of Tobramycin against M. fortuitum ATCC 6841 whereas 1-3 and 21 had positive response against M. tuberculosis H37Rv at varying degrees. Compound 21 was identified as the most potent derivative of the 1-22 series by an MIC value of 6.25 microg/mL and selectivity index of 1.6

A rapid, sensitive high performance liquid chromatographic method for the determination of meropenem in pharmaceutical dosage form, human serum and urine

A new, simple, precise and rapid high performance liquid chromatographic method was developed for the determination of meropenem in human serum, urine and pharmaceutical dosage forms. Chromatography was carried out on an LC18 column using a mixture of 15 mM KH2PO4:acetonitrile:methanol (84:12:4; v/v/v), adjusted to pH 2.8 with H3PO4 The proposed method was conducted using a reversed-phase technique, UV monitoring at 307.6 nm and cefepime as an internal standard. The: retention times were 5.98 and 7.47 min for cefepime and meropenem, respectively. The detector response was linear over the concentration range of 50-10,000 ng/mL. The detection Limit of the procedure was found to be 22 ng/mL. The detection limit for meropenem in human plasma was 108.4 ng/mL and the corresponding value in human urine was 179.3 ng/mL. No interference from endogenous substances in human serum, urine and pharmaceutical preparation was observed. The proposed method is sufficiently sensitive for determination of the concentrations of meropenem and may have clinical application for its monitoring in patients receiving the drug. Copyright (C) 2001 John Wiley & Sons, Ltd

Metabolic and chemical studies on N-(4-chlorobenzyl)-N'-benzoylhydrazine

The in vitro hepatic microsomal metabolism of N-(4-chlorobenzyl)-N'-benzoylhydrazine (CBBAH), a model compound representing N-alkyl substituted hydrazides, was studied using hepatic washed rat microsomal preparations fortified with NADPH to identify the possible N-oxidative, N-dealkylated and hydrolytic metabolites. CBBAH and its potential metabolites were prepared, characterized using spectroscopic techniques and then separated using a reversed phase HPLC system with UV detection at 254 nm. CBBAH was chemically converted to the corresponding hydrazone by m-chloroperbenzoic acid (m-CPBA) oxidation. CBBAH was incubated with rat microsomal preparations in the presence of NADPH, extracted into dichloromethane and evaporated finally under nitrogen. The TLC and HPLC results from the metabolic experiments showed that CBBAH produced the corresponding hydrolytic and N-dealkylated metabolites together with the corresponding hydrazone

The structure - Antituberculosis activity relationships study in a series of 5-(4-aminophenyl)-4-substituted-2,4-dihydro-3h-1,2,4- triazole-3-thione derivatives. A combined Electronic- Topological and Neural Networks approach

Antituberculosis activity of several 5-(4-aminophenyl)-4-alkyl/ aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones (1-9) and their thiourea derivatives (10-31) were screened for their antimycobacterial activities against Mycobacterium tuberculosis H37Rv using the BACTEC 460 radiometric system. Of the synthesized compounds, 10-12, 30 were the most active derivatives exhibiting more than 90% inhibition of mycobacterial growth at 12.5 μg/mL. Structure-activity relationships study was performed for the given series by using the Electronic-Topological Method combined with Neural Networks (ETM-NN). A system of prognosis was developed as the result of training associative neural network (ASNN) using weights of pharmacophoric fragments as descriptors. Descriptors were calculated by the projection of ETM compound and pharmacophoric fragments on the elements of Kohonen's self-organizing maps (SOM). From the detailed analysis of all compounds under study, the necessary requirements for a compound to possess antituberculosis activity were formulated. The analysis have shown that any requirements violation for a molecule implies a considerable decrease or even complete loss of its activity. © 2006 Bentham Science Publishers Ltd

Synthesis of some 3-(Arylalkylthio)-4-alkyl/aryl-5-(4-aminophenyl)-4H-1,2, 4-triazole derivatives and their anticonvulsant activity

A series of novel 3-{[(substituted phenyl)methyl]thio}-4-alkyl/aryl-5-(4- aminophenyl)-4H-1,2,4-triazoles 11-20 and several related Schiff's bases, 3-{[(substituted phenyl)-methyl]thio}-4-alkyl/aryl-5-{[[(substituted phenyl/5-nitro-2-furyl)methylene]amino]-phenyl}-4H-1,2,4-triazoles 21-31 were synthesized for evaluation of their biological properties. Structures of the synthesized compounds were confirmed by the use of their spectral data besides elemental analysis. All compounds were evaluated for their anticonvulsant activity by maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and neurotoxicity (NT) screens. A number of triazole derivatives, exhibited protection after intraperitoneal administration at the dose of 100 and 300 mg/kg in one or both models employed. Compounds 12, 13 and 14 were subjected to oral MES screening in rats at 30 mg/kg and were observed to protect 50% of the animals employed in the experiment. Antimicrobial and antituberculosis activity of these compounds 11-31 were also screened. Some of the tested compounds showed marginal activity against M. tuberculosis H37 Rv. © 2004 Published by Elsevier SAS