Microtubule destabilising activity of selected 7-methoxy-2-phenylbenzo[b]furan derivative against primary and metastatic melanoma cells

Herein, we report the results of Anticancer screening of two 2-phenylbenzo[b]furan derivatives functionalised at the 3-position with 4-hydroxy-3,5-dimethoxybenzoyl (BF2) or 3,4,5-trimethoxybenzoyl (BF3) against 60 different Cancer cell lines. The results confirmed the Anticancer potential of the tested compounds against different Cancer cell types, especially colon Cancer, brain Cancer and melanoma. BF3 was defined as the most potent (also as a tubulin polymerisation inhibitor). Its Anticancer activity against melanoma cell lines that originated from different stages, i.e., primary skin-derived A375 and metastatic WM9/MDA-MB-435S, was evaluated (as the clinical success of melanoma therapy strictly depends on the disease stage). Moreover, to determine the BF3 mode of action and its effect on cell proliferation, intracellular microtubule networks, cell cycle phase distribution and Apoptosis were evaluated. Our study revealed that BF3 inhibited cell proliferation in a dose-dependent manner, with IC₅₀ yielding 0.09 ± 0.01 μM, 0.11 ± 0.01 μM and 0.18 ± 0.05 μM for A375, MDA-MB435S and WM9, respectively. The strong antiproliferative activity of compound BF3 correlated well with its inhibitory effect on tubulin polymerisation. Molecular docking proved that BF3 belongs to the colchicine binding site inhibitors (CBSIs), and experimental studies revealed that it disturbs cell cycle progression leading to G2/M arrest and Apoptosis.

Anticancer agents; Antitubulin agents; Benzofurans; Colchicine-binding site inhibitors; Melanoma.