Synthesis, anti-inflammatory and molecular docking of some new 1,2,4-triazolobenzimidazol-3-yl acetone thiosemicarbazone cyclized derivatives as PLA-2 inhibitors

Abstract

The present work is carried out for the synthesis and evaluation of some new 1,3,4-thiadiazolines, 1,3-thiazolines and 1,3-thiazolidin-4-ones linked to 1,2,4-triazolo[1,5-a]benzimidazole as anti-inflammatory agents. Structure elucidation of these compounds was confirmed by IR, ¹H-NMR, and mass spectrometry along with elemental microanalyses. All new compounds were tested for their anti-inflammatory activity in comparison to indomethacin (INM) where some of them showed promising results comparable to INM at 4 hours interval. The most active anti-inflammatory compounds (4b, 8c and 9a) were examined on gastric mucosa and didn’t show any gastric ulcerogenic effect compared with the reference INM. Moreover, LD₅₀ of compounds (4b and 9a) were determined in mice; they were found non toxic up to 400 mg Kg^–1 (i.p.). Also, docking simulation of some compounds into PLA2 active sites was studied.