Synthesis, biological evaluation and 3D-QSAR studies of novel 5-phenyl-1H-pyrazol cinnamamide derivatives as novel antitubulin agents

•24 novel 5-phenyl-1H-pyrazol cinnamamide derivatives had been synthesized.•The compounds were evaluated for biological activities as tubulin inhibitors.•Compound 5j showed the most potent inhibitory activity.

A series of novel 5-phenyl-1H-pyrazol derivatives (5a–5x) containing cinnamamide moiety were synthesized and their biological activities as potential tubulin polymerization inhibitors were evaluated. Among them, compound 5j exhibited the most potent inhibitory activity with an IC50 value of 1.02 μM for tubulin, which was superior to that of Colchicine (IC50 = 1.34 μM). Docking simulation was performed to insert compound 5j into the crystal structure of tubulin at colchicine binding site to determine the probable binding model. 3D-QSAR model was also built to provide more pharmacophore understanding that could be used to design new agents with more potent tubulin inhibitory activity.

Graphical abstractCompound 5j exhibited the most potent inhibitory activity with an IC50 value of 1.02 μM for tubulin, 0.35 μM for MCF-7, 0.62 μM for A549 and 0.57 μM for B16–F10.Figure optionsDownload full-size imageDownload as PowerPoint slide