Design and evaluation of novel N-substituent diphenylamine derivatives as tubulin colchicine binding site inhibitors.

Novel N-substituent diphenylamine derivatives as tubulin inhibitors targeting colchicine-binding site have been designed based on structural simplification and structural fusing strategy. Most designed compounds exhibited the moderate or potent antiproliferative activities against five cancer cell lines. Among them, compound 4k displayed the significant selectivity for osteosarcoma cells MG-63 and U2OS with the IC50 value of 0.08-0.14 μM. Further investigations verified 4k could inhibit tubulin polymerization by targeting colchicine binding site. Meanwhile, compound 4k not only effectively induced tumor cell cycle arrest at the G2/M phase, but also slightly induced cell apoptosis. These results indicated that N-substituent of diphenylamine derivatives are deserved for further development as tubulin colchicine binding site inhibitors. Copyright © 2024 Elsevier Ltd. All rights reserved.

Citation

Zhong Chen, Da-Wei Geng, Tang-Bo Yuan, Chen Yu, Da-Wei Cai, Yong Yin, Qiang Shen. Design and evaluation of novel N-substituent diphenylamine derivatives as tubulin colchicine binding site inhibitors. Bioorganic & medicinal chemistry letters. 2025 Jan 01;115:130031

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PMID: 39557311

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