Synthesis, characterization, COX1/2 inhibition and molecular modeling studies on novel 2-thio-diarylimidazoles.

Heterocyclic compounds with diaryl substituents have been a milestone approach for selective cyclooxygenase 2 (COX 2) inhibition by bioisosteric replacements and modifications. It is also known that thiazole derivatives have different pharmacological activities. In this study, nine novel 2-[(1,5-diphenyl-1 H -imidazole-2-yl)thio]-N-(thiazole-2-yl)acetamide derivatives (Compound 1-9 ) were synthesized via the reaction of 1,5-disubstitued phenyl-imidazole-2-thiole and N -thiazole acetamide. The inhibitory effects of COX-1 and COX-2 enzymes were tested for the synthesized compounds. Enzyme-ligand interactions of the most active compound on COX subtypes were elucidated by molecular modeling studies. The percent inhibitory effect for compound 1 , which is the naked derivative among all the compounds, was found to be the most active on COX-2 at 10 μM concentration ( C1 COX-2 : 88%, SC-560 COX-2 : 98.2%, C1 COX-1 : 60.9%); whereas compound 9 showed the highest inhibitory effect and was found to be the most selective derivative on COX-1 isoenzyme ( C9 COX-1 : 85%, DuP-697 COX-1 : 97.2%, C9 COX-2 : 57.9%).