New chalcones and thiopyrimidine analogues derived from mefenamic acid: microwave-assisted synthesis, anti-HIV activity and cytotoxicity as antileukemic agents

Abstract

AbstractThe development of new HIV non-nucleoside reverse transcriptase inhibitors offers the possibility of generating structures of increased potency. To this end, coupling of mefenamic acid (4) with 4-amino-acetophenone (6) in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine (DMAP) reagents afforded 4-(acetyphenyl)-2-((2,3-dimethylphenyl)amino)benzamide (7). Analogously, treatment of mefenamyl chloride (5) prepared from4with6under microwave irradiation (MWI) afforded7. A new series of substituted chalconyl-incorporated amide derivatives of mefenamic acid8–13were synthesized from condensation of7with various substituted benzaldehydes via the Claisen–Schmidt reaction. Treatment of8and11with thiourea in a basic medium afforded the thiopyrimidine analogues14and15, respectively. The newly synthesized compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. Compounds9and11showed cytotoxicity values of 2.17 and 2.06 μm, respectively, against mock-infected MT-4 cells (C type adult T leukemia cells), which considered to be promising antileukemic agents.