Design, Synthesis, and Antitumor Activity of Erianin Derivatives

Abstract

Erianin, despite its potent anticancer effects against various cancer cell lines, suffers from poor bioavailability due to limited solubility and rapid metabolism. To overcome these limitations, a series of novel erianin derivatives were designed, synthesized, and evaluated for their biological activities against HeLa, MDA-MB-231, and A498 cancer cell lines. Among these derivatives, compound 8j, 4-[6,7-dimethoxy-3,4-dihydro­isoquinolin-2(1H)-yl]-N-(4-methoxybenzyl)-4-oxo-N-(3,4,5-trimethoxyphenyl)butanamide, demonstrated the highest selectivity and most potent activity against HeLa cells with an IC₅₀ value of 7.53±3.57 μM. Compound 8j significantly inhibited the adhesion, proliferation, migration, and invasion of HeLa cells in a dose-dependent manner. Preliminary pharmacokinetic evaluations suggest favorable absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties consistent with drug-like behavior. Molecular docking studies further revealed that 8j binds to the colchicine-binding site of tubulin, indicating its potential mechanism of action. These findings suggest that compound 8j is a promising lead candidate for the development of novel anticancer agents targeting the colchicine-binding site on tubulin.