Evaluation of 4-phenylamino-substituted naphthalene-1,2-diones as tubulin polymerization inhibitors

Bioorg Med Chem Lett. 2018 Oct 1;28(18):3057-3063. doi: 10.1016/j.bmcl.2018.07.047.

Honghao Yang ¹, Baijiao An ², Xingshu Li ³, Wei Zeng ⁴

Affiliations

1 Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510641, China.
2 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
3 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. Electronic address: lixsh@mail.sysu.edu.cn.
4 Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510641, China. Electronic address: zengwei@scut.edu.cn.

PMID: 30093295 DOI: 10.1016/j.bmcl.2018.07.047

Abstract

A series of 4-phenylamino-substituted naphthalene-1,2-dione derivatives were prepared and evaluated as effective antiproliferative agents. MTT assays showed that the compounds with a methyl group on the nitrogen linker exhibited potent antiproliferative activities against human Cancer cells. The mechanistic study revealed that these compounds could induce mitochondrial depolarization, which resulted in intracellular ROS production, and they also acted as tubulin polymerization inhibitors. Moreover, the typical compound could arrest A549 cells in the G2/M phase, resulting in cellular Apoptosis and induced mitotic arrest in A549 cells through disrupting microtubule dynamics.

Keywords

Antitumor agents; Mechanism; Reactive oxygen species; Tubulin polymerization inhibitors.

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