• Journal of the Korean Chemical Society
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• v.54 no.1
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• pp.77-87
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• 2010

Hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) has been an increasing problem worldwide since the initial reports over 40 years ago. To examine new drug leads with potential antibacterial activities, Various N'-[(-3-substituted-4-oxo-1,3-thiazolidin-2-ylidene]-4-hydroxy benzohydrazide (4a-4.i) and N'-[-(3,4-disubstituted)-1,3-thiazolidin-2ylidene)]-4-hydroxybenzohydrazide from (5.a-5.i) to (10.a-10.i) were synthesized using appropriate synthetic route. The entire test compounds (4.a-4.i) and from (5.a-5.i) to (10.a-10.i) were assayed in vitro against s. aureus strain. The minimum inhibitory concentration (MIC) was determined for test compounds and for reference standards. The test compounds showed significant antibacterial activity against the strains used, when tested in vitro. In general, p-hydroxybenzohydrazide ring and substituted thiazoline ring are essential for antimicrobial activity. Among the compounds tested, compounds 6.f, 7.g, 9.f and 10.f, 10 i were found to be most potent. The test compounds were found nontoxic upto the dose level of 2000 ${\mu}g$/mL. The intact compounds were then subjected for 3D-QSAR studies. 3D-QSAR study based on the principal of alignment of pharmacophoric features by Schrodinger PHASE module. The 3D-QSAR study allowed us to confirm the preferential binding mode of p-hydroxybenzohydrazide inside the active site.

• Journal of the Korean Chemical Society
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• v.56 no.2
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• pp.236-245
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• 2012

The main mycobacterial infection in human is tuberculosis caused by Mycobacterium tuberculosis. Tuberculosis is the leading infectious cause of death in the world. Therefore there is continuing and compelling need for new and improved treatment for tuberculosis. The entire logic towards design of new compounds containing 4-hydroxy-N'-(1,3-thiazoldin- 2-yldene)benzohydrazide moiety is basically for superior antimycobacterial activity. The recent advances in QSAR and computer science have provided a systematic approach to design a structure of any compound and further, the biological activity of the compound can be predicted before synthesis. The 3D-QSAR studies for the set of 4-hydroxy-N'-(1,3-thiazoldin- 2-yldene)benzohydrazide and their derivatives were carried out by using V-life MDS (3.50). The various statistical methods such as Multiple Linear Regression (MLR), Partial Least Square Regression (PLSR), Principle Component Regression(PCR) and K nearest neighbour (kNN) were used. The kNN showed good results having cross validated $r^2$ 0.9319, $r^2$ for external test set 0.8561 and standard error of estimate 0.2195. The docking studies were carried out by using Schrodinger GLIDE module which resulted in good docking score in comparison with the standard isoniazid. The designed compounds were further subjected for synthesis and biological evaluation. Antitubercular evaluation of these compounds showed that (4.a), (4.d) and (4.g) found as potent inhibitor of H37RV.