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

• Published in: Bioorganic & medicinal chemistry letters Vol. 43; p. 128112
• Main Authors: Nesaragi, Aravind R., Kamble, Ravindra R., Dixit, Shruti, Kodasi, Barnabas, Hoolageri, Swati R., Bayannavar, Praveen K., Dasappa, Jagadeesh Prasad, Vootla, Shyamkumar, Joshi, Shrinivas D., Kumbar, Vijay M.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.07.2021; Elsevier
• Subjects: 1,3,4-Oxadiazole; Antioxidant; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Coumarin; COX-2 inhibitors; Life Sciences & Biomedicine; Mercapto benzoxazole; Microwave; Molecular docking; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; COX-2 inhibitors; Mercapto benzoxazole; 1,3,4-Oxadiazole; Microwave; Antioxidant; Coumarin; Molecular docking; VITRO; ANTIINFLAMMATORY ACTIVITY; DESIGN; ACID; 4-Oxadiazole; 1; 3; ANTICANCER; DERIVATIVES; 1,3,4-oxadiazole
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2021.128112

[Display omitted] •Novel coumarin-4-yl-1,3,4-oxadiazolyl-2-mercaptobenzoxazoles 8i-t are reported.•Microwave synthesis resulted shorter reaction times, excellent yields with high purity.•The reported compounds demonstrated high selectivity against COX-2.•All the compounds exhibited strong antioxidant activity. 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.