Synthesis of novel 2-mercapto benzothiazole and 1,2,3-triazole based bis-heterocycles: Their anti-inflammatory and anti-nociceptive activities

A focused library of novel bis-heterocycles encompassing 2-mercapto benzothiazole and 1,2,3-triazoles were synthesized using click chemistry approach. The synthesized compounds have been tested for their anti-inflammatory activity by using biochemical cyclooxygenase (COX) activity assays and carrageenan-induced hind paw edema. Among the tested compounds, compound 4d demonstrated a potent selective COX-2 inhibition with COX-2/COX-1 ratio of 0.44. Results from carrageenan-induced hind paw edema showed that compounds 4a, 4d, 4e and 4f posses significant anti-inflammatory activity as compared to the standard drug Ibuprofen. The compounds showing significant activity were further subjected to anti-nociceptive activity by writhing test. These four compounds have shown comparable activity with the standard Ibuprofen. Further ulcerogenic studies shows that none of these compounds causing gastric ulceration.

Graphical abstractNovel bis-heterocycles encompassing 2-mercapto benzothiazole and 1,2,3-triazoles demonstrated a potent selective COX-2 inhibition and significant anti-inflammatory activity as compared to the standard drug Ibuprofen without causing any ulceration.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► New bis-heterocycles bearing 2-mercapto benzothiazole and triazoles were synthesized. ► Some of the compounds demonstrated a potent selective COX-2 inhibition. ► Molecular docking study also confirms strong binding potential towards COX-2. ► Significant anti-inflammatory activity in vivo was observed as compared to Ibuprofen. ► Compounds 4d and 4e are showing better analgesic activity compared to Ibuprofen.