4′-Alkoxyl substitution enhancing the anti-mitotic effect of 5-(3′,4′,5′-substituted)anilino-4-hydroxy-8-nitroquinazolines as a novel class of anti-microtubule agents

Mitosis inhibitors are powerful anticancer drugs. Based on a novel anti-microtubule agent of 5-(4′-methoxy)anilino-4-hydroxy-8-nitroquinazoline, a series of 5-(3′,4′,5′-substituted)anilino-4-hydroxy-8- nitroquinazolines were designed and synthesized to investigate the effect of the substitution on the inhibitory activity against mitotic progression of tumor cells. The large alkoxyl substitution on the 4′-position of 5-anilino ring is beneficial for the potency. The 5-(3′,4′,5′-trimethoxy)anilino-8-nitroquinazoline (1h) displays an overwhelming activity in arresting the cells at the G2/M phase, providing a promising new template for further development of potent microtubule-targeted anti-mitotic drugs.

The design and synthesis of 5-(3′,4′,5′-substituted)anilino-4-hydroxy-8- nitroquinazolines as a new class of mitosis inhibitors was reported. The alkoxyl substitution on 3′,4′-positions of 5-anilino portion was found favorable for the potency. So, the best activity was exhibited by the 5-(3′,4′,5′-trimethoxy)anilino-8-nitroquinazoline (1h) in arresting 81% of the tumor cells at the G2/M phase at the concentration of 50 μM.Figure optionsDownload as PowerPoint slide