Synthesis and Anticancer Activity of Metformin-Phenolic Acid Conjugates.

Abstract

The leading cause of death worldwide is cancer. Several studies suggest phenolic acids and metformin as potential cancer treatment options because of their biological and therapeutic properties. So, we synthesized some novel metformin-phenolic acid conjugates. We used an acid-base neutralization method to extract the metformin-free base. N, N`-dicyclohexylcarbodiimide (DCC)-4-dimethylaminopyridine (DMAP) coupling of phenolic/aromatic acids (benzoic acid, cinnamic acid, caffeic acid, ferulic acid, gallic acid, para-hydroxybenzoic acid, para coumaric acid, protocatechuic acid, salicylic acid, and vanillic acid) with metformin was performed to produce metformin phenolic acid conjugates (M1-M10). We evaluated the structures using 1H-NMR, 13C-NMR, FT-IR, and MS. All newly synthesized metformin phenolic acid conjugates were evaluated for their in vitro anti-cancer activity. Metformin phenolic acid conjugates were synthesized and showed a range of inhibitory effects. The metformin-caffeic acid conjugate [(E)-3-(3,4-dihydroxyphenyl)-N-(N,N-dimethylcarbamimidoyl)carbamimidoyl)acrylamide] (M3) (IC50: 5.47±2.72 μg/ml and 4.42±2.15 μg/ml) showed the best anticancer activity against MDA-MB-468 and A549 cancer cell lines.