Synthesis, molecular docking with COX 1& II enzyme, ADMET screening and in vivo anti-inflammatory activity of oxadiazole, thiadiazole and triazole analogs of felbinac
Based on the core structure of Felbinac drug, three series (4a–d, 5a–d and 6a–n) of five membered heterocyclic derivatives containing three heteroatoms were designed and synthesized starting from Felbinac. In the rational design of the target molecules, the biphenyl ring along with the methylene bri...
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doaj-f314182d2c8d4c9b91f2638244e2641d2020-11-24T22:14:49ZengElsevierJournal of Saudi Chemical Society1319-61032018-05-01224469484Synthesis, molecular docking with COX 1& II enzyme, ADMET screening and in vivo anti-inflammatory activity of oxadiazole, thiadiazole and triazole analogs of felbinacShah Alam Khan0S. Monawwar Imam1Aftab Ahmad2Syed Hussain Basha3Asif Husain4Department of Pharmacy, Oman Medical College, Muscat, OmanDepartment of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India; Intellectual Property & Technology Licensing, King Saud University, Riyadh, Saudi ArabiaHealth Information Technology Department, Jeddah Community College, King Abdulaziz University, Jeddah 21589, Saudi ArabiaInnovative Informatica Technologies, Hyderabad 500 049, Telangana, IndiaDepartment of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India; Corresponding author at: Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard University, New Delhi 110 062, India.Based on the core structure of Felbinac drug, three series (4a–d, 5a–d and 6a–n) of five membered heterocyclic derivatives containing three heteroatoms were designed and synthesized starting from Felbinac. In the rational design of the target molecules, the biphenyl ring along with the methylene bridge of felbinac was retained while the carboxyl group was substituted with biologically active substituents like 1,2,4-triazole, 1,3,4-thiadiazole and 1,3,4-oxadiazole, with an intent to obtain novel, better and safer anti-inflammatory agents with improved efficacy. The prepared molecules were then investigated for their anti-inflammatory, ulcerogenicity and analgesic activity in experimental animals. The tested compounds exhibited varying degrees of inflammatory activity (25.21–72.87%), analgesic activity (27.50–65.24%) and severity index on gastric mucosa in the range of 0.20–0.80 in comparison to positive control felbinac (62.44%, 68.70% and 1.5, respectively). Among all the prepared compounds, 2-(biphenyl-4-ylmethyl)-5-(4-chlorophenyl)-1,3,4-oxadiazole (6c) emerged as the most potent NSAID compound exhibiting the highest anti-inflammatory activity (72.87% inhibition) and analgesic activity (65.24%) along with the least severity index on gastric mucosa (0.20). Further, molecular docking on cyclooxygenase and in silico ADME-Toxicity prediction studies also supported the experimental biological results and indicated that 6c has a potential to serve as a drug candidate or lead compound for developing novel anti-inflammatory and analgesic therapeutic agent(s) with minimum toxicity on gastric mucosa. Keywords: Felbinac, Oxadiazole, Triazole, Thiadiazole, Anti-inflammatory, Molecular dockinghttp://www.sciencedirect.com/science/article/pii/S1319610317300649 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shah Alam Khan S. Monawwar Imam Aftab Ahmad Syed Hussain Basha Asif Husain |
spellingShingle |
Shah Alam Khan S. Monawwar Imam Aftab Ahmad Syed Hussain Basha Asif Husain Synthesis, molecular docking with COX 1& II enzyme, ADMET screening and in vivo anti-inflammatory activity of oxadiazole, thiadiazole and triazole analogs of felbinac Journal of Saudi Chemical Society |
author_facet |
Shah Alam Khan S. Monawwar Imam Aftab Ahmad Syed Hussain Basha Asif Husain |
author_sort |
Shah Alam Khan |
title |
Synthesis, molecular docking with COX 1& II enzyme, ADMET screening and in vivo anti-inflammatory activity of oxadiazole, thiadiazole and triazole analogs of felbinac |
title_short |
Synthesis, molecular docking with COX 1& II enzyme, ADMET screening and in vivo anti-inflammatory activity of oxadiazole, thiadiazole and triazole analogs of felbinac |
title_full |
Synthesis, molecular docking with COX 1& II enzyme, ADMET screening and in vivo anti-inflammatory activity of oxadiazole, thiadiazole and triazole analogs of felbinac |
title_fullStr |
Synthesis, molecular docking with COX 1& II enzyme, ADMET screening and in vivo anti-inflammatory activity of oxadiazole, thiadiazole and triazole analogs of felbinac |
title_full_unstemmed |
Synthesis, molecular docking with COX 1& II enzyme, ADMET screening and in vivo anti-inflammatory activity of oxadiazole, thiadiazole and triazole analogs of felbinac |
title_sort |
synthesis, molecular docking with cox 1& ii enzyme, admet screening and in vivo anti-inflammatory activity of oxadiazole, thiadiazole and triazole analogs of felbinac |
publisher |
Elsevier |
series |
Journal of Saudi Chemical Society |
issn |
1319-6103 |
publishDate |
2018-05-01 |
description |
Based on the core structure of Felbinac drug, three series (4a–d, 5a–d and 6a–n) of five membered heterocyclic derivatives containing three heteroatoms were designed and synthesized starting from Felbinac. In the rational design of the target molecules, the biphenyl ring along with the methylene bridge of felbinac was retained while the carboxyl group was substituted with biologically active substituents like 1,2,4-triazole, 1,3,4-thiadiazole and 1,3,4-oxadiazole, with an intent to obtain novel, better and safer anti-inflammatory agents with improved efficacy. The prepared molecules were then investigated for their anti-inflammatory, ulcerogenicity and analgesic activity in experimental animals. The tested compounds exhibited varying degrees of inflammatory activity (25.21–72.87%), analgesic activity (27.50–65.24%) and severity index on gastric mucosa in the range of 0.20–0.80 in comparison to positive control felbinac (62.44%, 68.70% and 1.5, respectively). Among all the prepared compounds, 2-(biphenyl-4-ylmethyl)-5-(4-chlorophenyl)-1,3,4-oxadiazole (6c) emerged as the most potent NSAID compound exhibiting the highest anti-inflammatory activity (72.87% inhibition) and analgesic activity (65.24%) along with the least severity index on gastric mucosa (0.20). Further, molecular docking on cyclooxygenase and in silico ADME-Toxicity prediction studies also supported the experimental biological results and indicated that 6c has a potential to serve as a drug candidate or lead compound for developing novel anti-inflammatory and analgesic therapeutic agent(s) with minimum toxicity on gastric mucosa. Keywords: Felbinac, Oxadiazole, Triazole, Thiadiazole, Anti-inflammatory, Molecular docking |
url |
http://www.sciencedirect.com/science/article/pii/S1319610317300649 |
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