Design and Synthesis of 4(1H)-quinolone Derivatives as Autophagy Inducing Agents by Targeting ATG5 Protein

Author(s): Yifan Jia, Difei Yu, Qiuhua Huang, Xiaodong Zhang, Liqin Qiu, Rihui Cao*, Runlei Du*, Wenbin Liu*.

Journal Name: Letters in Drug Design & Discovery

Volume 17 , Issue 7 , 2020

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Graphical Abstract:


Background: Quinolines have been characterized as a class of potential antitumor agents, and a large number of natural and synthetic quinolines acting as antitumor agents were reported.

Methods: A series of 7-chloro-4(1H)-quinolone derivatives were synthesized. The antiproliferative effect of these compounds was evaluated by MTT assay against five human tumor cell lines. The mechanism of action of the selected compound 7h was also investigated.

Results and Discussion: Most of the compounds had more potent antiproliferative activities than the lead compound 7-chloro-4(1H)-quinolone 6b. Compound 7h was found to be the most potent antiproliferative agent against human tumor cell lines. Further investigation demonstrated that compound 7h triggered ATG5-dependent autophagy of colorectal cancer cells by promoting the functions of LC3 proteins.

Conclusion: These results were useful for designing and discovering more potent novel antitumor agents endowed with better pharmacological profiles.

Keywords: Synthesis, quinolone, antiproliferative, autophagy, mechanism of action, ATG5 protein.

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Article Details

Year: 2020
Page: [884 - 890]
Pages: 7
DOI: 10.2174/1570180816666191122113045
Price: $65

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