Novel fluorinated amino acid derivatives as potent antitumor agents against MCF-7 and HepG2 cells: Synthesis, characterization, in vitro assays and molecular docking studies

Abstract

To tackle healthcare challenges including neoplastic, cardiac, neurological disease and infectious disease faced by the world community, it is highly demanding to design and synthesize innovative molecules. Herein using a variety of amino acids and fluorinated aromatic amines, we have designed and synthesized novel fluorinated amino acid derivatives (1a–6b) as potential anticancer agents. Among synthesized fluorinated compounds 1a, 1b, and 3b showed potent anticancer activity against MCF-7 cancer cell lines. Similarly, compounds 1b and 2a showed moderate activity against HepG2 cancer cell lines. Compound 1b was found to be the most effective cytotoxic compound against MCF-7 breast cancer cells with a mean IC50 value of 11.63 µM and also effective against HepG2 liver cancer cells with a mean IC50 value of 34.10 µM. Additionally, a molecular docking study was carried out to determine the molecular binding affinity of the synthesized fluorinated derivatives. The compound 1b showed the highest binding affinity (binding energy: −12.6 kcal/mol) which interacted more effectively with PRO 385 (4.75 Å) than standard drug doxorubicin binding affinity (binding energy: −10.4 kcal/mol).