Discovery and molecular modeling of novel 1-indolyl acetate – 5-Nitroimidazole targeting tubulin polymerization as antiproliferative agents

• 18 novel 1-indolyl acetate-5-nitroimidazole 3a–3r analogs of combretastatin A-4 have been synthesized.
• Their biological activities were evaluated as potential tubulin polymerization inhibitors.
• Compound 3p displayed strong antitumor activity.

A series of 18 novel 1-indolyl acetate-5-nitroimidazole 3a–3r were designed, synthesized, and evaluated for their in vitro biological activities as potential tubulin polymerization inhibitors. Among these compounds, 3p displayed strong antitumor activity with IC50 of 2.00, 1.05, 0.87 μM against A549, Hela and U251 respectively, and also showed the most potent PLK1 inhibitory activity with IC50 of 2.4 μM. Molecular docking studies within the colchicine binding site of tubulin were in good agreement with the tubulin polymerization inhibitory data and confirmed the importance of the configuration of the synthesized 1-indolyl acetate-5-nitroimidazolefor potential tubulin polymerization inhibitors.

A series of 18 novel 1-indolyl acetate-5-nitroimidazole 3a–3r analogs of combretastatin A-4 were designed, synthesized, and evaluated for their in vitro biological activities as potential tubulin polymerization inhibitors.Figure optionsDownload as PowerPoint slide