Design, synthesis, and biological evaluation of 2,3‐diphenyl‐cycloalkyl pyrazole derivatives as potential tubulin polymerization inhibitors.

Several novel cycloalkyl‐fused 2,3‐diaryl pyrazole derivatives were designed, synthesized, and evaluated as potential anti‐tubulin agents. Compound A10 exhibited the most potent antiproliferative activity against a panel of cancer lines (IC50 = 0.78–2.42 μM) and low cytotoxicity against 293T & L02 (CC50 values of 131.74 and 174.89 μM, respectively). Moreover, A10 displayed inhibition of tubulin polymerization in vitro, arrested the G2/M phase of the cell cycle, changed morphology of tubulin, increased intracellular reactive oxygen species, and induced apoptosis of HeLa cells. Docking simulation and 3D‐QSAR models were performed to elaborate on the anti‐tubulin mechanism of the derivatives. The inhibition of monoclonal colony formation provided more intuitional data to verify the possibility of A10 as a novel tubulin assembling inhibitor. [ABSTRACT FROM AUTHOR]