Focused library design and synthesis of 2-mercapto benzothiazole linked 1,2,4-oxadiazoles as COX-2/5-LOX inhibitors

• Published in: Journal of molecular structure 2018-05, Vol.1159, p.193-204
• Main Authors: Yatam, Satayanarayana, Gundla, Rambabu, Jadav, Surender Singh, Pedavenkatagari, Narayana reddy, Chimakurthy, Jithendra, Rani B, Namratha, Kedam, Thyagaraju
• Format: Article
• Language: English
• Subjects: 1,2,4-Oxadiazole; 5-LOX; Anti-inflammatory; Anti-oxidant; COX-2; Design; Docking
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2018.01.060

Mercapto benzothiazole linked 1,2,4-oxadiazole derivatives were designed (4a-u) as new anti-inflammatory agents using bioisosteric approach and docking studies. The docking results clearly indicated that the compounds 4a-u shown good docking interaction towards COX-2 enzyme. In silico drug-like properties were also calculated for compounds (4a-u) and exhibited significant H-bond acceptor ratio. All compounds were synthesized and biologically evaluated using in vitro COX-1, COX-2 and 5-LOX assays. Compound 4k and 4q (IC50 = 6.8 μM and IC50 = 5.0 μM) found to be potent, selective COX-2 inhibitors and display better anti-inflammatory activity than standard Ibuprofen. Compound 4l and 4e found to be potent inhibitors against 5-LOX (IC50 = 5.1 μM and IC50 = 5.5 μM). The in vivo anti-inflammatory activity studies shown that the compounds 4q and 4k effectively reducing the paw edema volume at 3h and 5h than standard drug Ibuprofen. The DPPH radical scavenging activity provided anti-oxidant activity of compound 4e (IC50 = 25.6 μM) than reference standard Ascorbic acid. Design approach of 2-mercapto benzothiazole linked 1,2,4 oxadiazoles. [Display omitted] •Focused library design and docking studies.•1,2,4-oxadiazole linked mercapto benzothiazole derivatives.•Synthesis and biological screening.•Selective COX-2 and potent 5-LOX inhibitors.