Green synthesis of therapeutically active 1,3,4-oxadiazoles as antioxidants, selective COX-2 inhibitors and their in silico studies

Aravind R Nesaragi; Ravindra R Kamble; Shruti Dixit; Barnabas Kodasi; Swati R Hoolageri; Praveen K Bayannavar; Jagadeesh Prasad Dasappa; Shyamkumar Vootla; Shrinivas D Joshi; Vijay M Kumbar

doi:10.1016/j.bmcl.2021.128112

Green synthesis of therapeutically active 1,3,4-oxadiazoles as antioxidants, selective COX-2 inhibitors and their in silico studies

Bioorg Med Chem Lett. 2021 Jul 1:43:128112. doi: 10.1016/j.bmcl.2021.128112. Epub 2021 May 13.

Affiliations

¹ Department of Studies in Chemistry, Karnatak University, Dharwad 580003, India.
² Department of Studies in Chemistry, Karnatak University, Dharwad 580003, India. Electronic address: ravichem@kud.ac.in.
³ Department of Biotechnology and Microbiology, Karnatak University, Dharwad 580003, India.
⁴ Department of Chemistry, Mangalore University, Mangalagangothri, Konaje 574199, India.
⁵ Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S.E.T.'s College of Pharmacy, Dharwad 580002, India.
⁶ Central Research Laboratory, Maratha Mandal's NGH Institute of Dental Sciences and Research Centre, Belagavi 590010, India.

PMID: 33991632
DOI: 10.1016/j.bmcl.2021.128112

Abstract

A modest, competent and green synthetic procedure for novel coumarinyl-1,3,4-oxadiazolyl-2-mercaptobenzoxazoles 8i-t has been reported. Analysis of the docked (PDB ID: 5IKR; A-Chain) poses of the compounds illustrated that they adopt identical conformations to the extremely selective COX-2 inhibitor. The biological outcomes as well as computational study suggested that the compounds originated to have elevated resemblance towards COX-2 enzyme than COX-1. The compounds 8i, 8l, 8q, 8r, 8s and 8t emerged as most potent and selective COX-2 inhibitors in contrast with Mefenamic acid. The selectivity index of 8l, 8n and 8r was respectively found to be 33.95, 20.25 and 24.98 which manifested their high selectivity against COX-2. Interestingly, the compounds which were active as COX-2 inhibitors were also active as antioxidant agents.

Keywords: 1,3,4-Oxadiazole; Antioxidant; COX-2 inhibitors; Coumarin; Mercapto benzoxazole; Microwave; Molecular docking.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antioxidants / chemical synthesis
Antioxidants / chemistry
Antioxidants / pharmacology*
Biphenyl Compounds / antagonists & inhibitors
Cyclooxygenase 2 / metabolism*
Cyclooxygenase 2 Inhibitors / chemical synthesis
Cyclooxygenase 2 Inhibitors / chemistry
Cyclooxygenase 2 Inhibitors / pharmacology*
Green Chemistry Technology*
Humans
Microwaves
Models, Molecular
Molecular Structure
Oxadiazoles / chemical synthesis
Oxadiazoles / chemistry
Oxadiazoles / pharmacology*
Picrates / antagonists & inhibitors

Substances

Antioxidants
Biphenyl Compounds
Cyclooxygenase 2 Inhibitors
Oxadiazoles
Picrates
1,1-diphenyl-2-picrylhydrazyl
Cyclooxygenase 2