Synthesis, cytotoxicity, and molecular docking of methylated (–)-epigallocatechin-3-gallate-4β-triazolopodophyllotoxin derivatives as novel antitumor agents

Abstract

A series of novel methylated (–)-epigallocatechin-3-gallate-4β-triazolopodophyllotoxin derivatives is synthesized by utilizing the click reaction. Evaluation of their cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480) using the MTT assay shows that most of these compounds exhibit weak cytotoxicity. It is observed that compound 12 shows the highest activity against A-549 cells with an IC50 value of 10.27 ± 0.90 μM. Molecular docking results suggested that this compound 12 has a higher binding affinity for epidermal growth factor receptor than for tubulin. Our findings support the utility of compound 12 as a novel compound for the further development of anticancer agents.