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-4-dimethylaminopyridine 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 proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, Fourier-transform infrared, and mass spectroscopy. All newly synthesized metformin phenolic acid conjugates were evaluated for their in vitro anticancer 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 and 4.42 ± 2.15 µg/mL) showed the best anticancer activity against MDA-MB-468 and A549 cancer cell lines.