Synthesis, molecular modeling and biological evaluation of guanidine derivatives as novel antitubulin agents.

A series of novel chalcone guanidine derivatives (4a-4q) have been designed and synthesized, and their biological activity were also evaluated as potential antiproliferative and antitubulin polymerization inhibitors. Compound 4q showed the most potent biological activity (IC₅₀ = 0.09 ± 0.01 μM for MCF-7 and IC₅₀ = 8.4 ± 0.6 μM for tubulin), which is comparable to the positive controls. Docking simulation was performed to position compound 4q into the colchicine binding site to determine the probable binding model, which suggested probable inhibition mechanism.