Abstract
A library of novel bis-heterocycles containing 2-mercaptobenzoxazole based 1,2,3-triazoles has been synthesized using click chemistry approach. The compound 4 exhibited the most potent in vivo anti-inflammatory activity with 66.66% and 61.11% inhibition in comparison to celecoxib which showed 72.22% and 65.55% inhibition after 3 h and 5 h respectively. The compounds 4 and 9 suppressed the COX-2 gene expression by 0.94 and 0.79 fold and exhibited a selective index (COX-1/COX-2) of 64.79 and 66.47 respectively in comparison to celecoxib (SI value of 75.56). The in silico molecular docking studies showed the interactions of these molecules with Tyr-59, Tyr-119 and Gly-121. When compared with the standard drug celecoxib, compounds 4, 5, 7, 9 and 16 did not cause any gastric ulceration.
A library of 2-mercaptobenzoxazole based 1,2,3-triazoles has been synthesized with an aim to develop new molecules with a potential to inhibit the increase in the levels of proinflammatory mediators like such as TNF-α, IL-1β, COX-2 and NO without inducing any gastric ulceration. [Display omitted]
•A library of 18 novel compounds has been synthesized using click chemistry.•TNF-α and COX-2 based in silico molecular docking studies are reported.•Compounds 4 and 9 suppressed the COX-2 expression by 0.94 and 0.79 fold respectively.•Compounds 4, 5, 7, 9 and 16 did not cause any gastric ulceration.