3,4,5-Trimethoxychalcones Tubulin Inhibitors with a Stable Colchicine Binding Site as Potential Anticancer Agents

The development of microtubule perturbing drugs is one the most promising anticancer therapeutic methods. Unfortunately, limitation such as drug resistance, adverse side effects, complex formulations and synthesis, limited bioavailability these has aroused search for a new molecule tubulin system. Different substituents chalcone were designed, synthesized, determined inhibition assembly toxicity in human cancer cell lines based on conventional colchicine site ligands computer model binding tubulin. A molecular docking study indicated that scaffold could fit similar orientation to natural product. 3,4,5-trimethoxyphenyl ring, which occupies same sub-cavity equivalent colchicine, appeared benefit ligand α,β-tubulin interaction. Several 3,4,5-trimethoxychalcone compounds demonstrated improved cytotoxicity against MCF-7 cells inhibited vitro potently colchicine. active 1 with IC50 6.18 ± 0.69 μM prevented proliferation at micromolar concentrations, causing destabilization mitotic arrest humans inhibiting breast cells.