Molecular Modeling, Synthesis and Pharmacological Evaluation of 1,3,4- Thiadiazoles as Anti-inflammatory and Analgesic Agents

Title:Molecular Modeling, Synthesis and Pharmacological Evaluation of 1,3,4- Thiadiazoles as Anti-inflammatory and Analgesic Agents

Volume: 12 Issue: 1

Author(s): Anas M. H. Shkair, Ashok K. Shakya, Nulgumnalli M. Raghavendra and Rajashri R. Naik

Affiliation:

Keywords: 1, 3, 4-thiadiazole, molecular modeling, docking studies, anti-inflammatory activity, analgesic activity, CADD, ulcerogenic potential.

Abstract: A series of novel substituted 2-amino-5-(1-(4-isobutylphenyl)ethyl)-1,3,4-thiadiazoles were designed, synthesized and evaluated as anti-inflammatory and analgesic agents. Compounds were characterized by elemental and spectroscopic analysis. Compounds possessing significant activities were screened for ulcerogenic activity. Compound-5 (2-(4-isobutylphenyl)-N-(5-(1-(4- isobutylphenyl)ethyl)-1,3,4-thiadiazol-2-yl)-propanamide) produces significant in vitro antiinflammatory activity (72.5%) as compared to ibuprofen (47.7%), while compound-3f (2-(Ncyclohexyl- N-methylamino)-N-(5-(1-(4-isobutylphenyl)-ethyl)-1,3,4-thiadiazol-2-yl)-acetamide) showed 64.1 % activity. Results indicate that compound-4 (N-(5-(1-(4-isobutyl-phenyl)-ethyl)-1,3,4-thiadiazol-2-yl)-acetamide) exhibited highest analgesic activity (69.8%), where as compound-5 possessed 65.5% activity. Structure based drug design was also investigated to reveal the mechanism of action and specificity of our compounds against COX-2 enzyme. Anti-inflammatory activity and ulcerogenic potential were in agreement with the molecular modeling studies carried out on cycloxygenase enzyme.

Cite this article as:

M. H. Shkair Anas, K. Shakya Ashok, M. Raghavendra Nulgumnalli and R. Naik Rajashri, Molecular Modeling, Synthesis and Pharmacological Evaluation of 1,3,4- Thiadiazoles as Anti-inflammatory and Analgesic Agents, Medicinal Chemistry 2016; 12 (1) . https://dx.doi.org/10.2174/1573406411666150608102236