Discovery of Novel Quinoline-Chalcone Derivatives as Potent Antitumor Agents with Microtubule Polymerization Inhibitory Activity

Wenlong Li, Feijie Xu, Wen Shuai, Honghao Sun, Hong Yao, Cong Ma, Shengtao Xu, Hequan Yao, Zheying Zhu, Dong Hua Yang, Zhe Sheng Chen, Jinyi Xu

Research output: Journal article publicationJournal articleAcademic researchpeer-review

57 Citations (Scopus)


A series of novel quinoline-chalcone derivatives were designed, synthesized, and evaluated for their antiproliferative activity. Among them, compound 24d exhibited the most potent activity with IC 50 values ranging from 0.009 to 0.016 μM in a panel of cancer cell lines. Compound 24d also displayed a good safety profile with an LD 50 value of 665.62 mg/kg by intravenous injection, and its hydrochloride salt 24d-HCl significantly inhibited tumor growth in H22 xenograft models without observable toxic effects, which was more potent than that of CA-4. Mechanism studies demonstrated that 24d bound to the colchicine site of tubulin, arrested the cell cycle at the G2/M phase, induced apoptosis, depolarized mitochondria, and induced reactive oxidative stress generation in K562 cells. Moreover, 24d has potent in vitro antimetastasis and in vitro and in vivo antivascular activities. Collectively, our findings suggest that 24d deserves to be further investigated as a potent and safe antitumor agent for cancer therapy.

Original languageEnglish
Pages (from-to)993-1013
Number of pages21
JournalJournal of Medicinal Chemistry
Issue number2
Publication statusPublished - 24 Jan 2019

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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