Design and synthesis of novel quinazolinones conjugated ibuprofen, indole acetamide, or thioacetohydrazide as selective COX-2 inhibitors: anti-inflammatory, analgesic and anticancer activities.

Novel quinazolinones conjugated with indole acetamide , ibuprofen ( or thioacetohydrazide ( and ) were designed to increase COX-2 selectivity. The three synthesised series exhibited superior COX-2 selectivity compared with the previously reported quinazolinones and their NSAID analogue and had equipotent COX-2 selectivity as celecoxib. Compared with celecoxib, , , and showed similar anti-inflammatory activity , while and showed superior inhibition of the inflammatory mediator nitric oxide, and showed greater antioxidant potential in macrophages cells. Moreover, all selected compounds showed improved analgesic activity and completely abolished the pain response. Additionally, compound showed anticancer activity in tested cell lines HCT116, HT29, and HCA7. Docking results were consistent with COX-1/2 enzyme assay results. studies suggest their high oral bioavailability. The overall findings for compounds ( and ) support their potential role as anti-inflammatory agents.