Synthesis, biological evaluation and molecular modeling of novel thienopyrimidinone and triazolothienopyrimidinone derivatives as dual anti-inflammatory antimicrobial agents

New thienopyrimidinone and triazolothienopyrimidinone derivatives have been synthesized. These compounds were subjected to anti-inflammatory and antimicrobial activity screening aiming to identify new candidates that have dual anti-inflammatory and antimicrobial activities. Compounds 5, 7 and 10a showed minimal ulcerogenic effect and high selectivity towards human recombinant COX-2 over COX-1 enzyme. Their docking outcome correlated with their biological activity and assured the high selectivity binding towards COX-2. In addition, they could act safely up to 80 mg/kg orally or 40 mg/kg parentrally. The antimicrobial screening showed that compound 10a displayed distinctive inhibitory effect on the growth of Escherichia coli comparable to that of ampicillin. Moreover, compounds 5, 7, 9 and 12a possessed 50% of the inhibitory activity of ampicillin against E. coll. Thus, compounds 5, 7 and 10a represent promising dual acting anti-inflammatory and antimicrobial agents. This work provides rewarding template enriching the chemical space for dual anti-inflammatory antimicrobial activities. (C) 2018 Elsevier Inc. All rights reserved.