Evaluation of 4-phenylamino-substituted naphthalene-1, 2-diones as tubulin polymerization inhibitors. Issue 18 (1st October 2018)

• Record Type: Journal Article
• Authors: Yang, Honghao; An, Baijiao; Li, Xingshu; Zeng, Wei
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 18(2018)
• Page Start: 3057
• Page End: 3063
• Publication Date: 2018-10-01
• Subjects: Antitumor agents -- Tubulin polymerization inhibitors -- Mechanism -- Reactive oxygen species; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.07.047
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: A series of 4-phenylamino-substituted naphthalene-1, 2-dione derivatives evaluated as effective antiproliferative agents. Some compounds exhibited potent antiproliferative activities. Mechanistic study revealed that compound3b acted as tubulin polymerization inhibitors. Compound3b could induce mitochondrial depolarization and resulted in intracellular ROS production. 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.