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Issue 10, 2017
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Identification of novel 3-nitroacridines as autophagy inducers in gastric cancer cells

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Abstract

Dysregulated autophagy is involved in various human disorders including cancer. An autophagy-associated cell death pathway can be seen as a back-up cell death mechanism in cancer cells that are deficient in the apoptosis pathway. Therefore, many attempts have been made to induce autophagy for anticancer therapy. Anti-apoptotic Bcl-2 family proteins Bcl-2 and Bcl-xL can inhibit autophagy via binding to the BH3-only protein Beclin 1, an essential autophagy stimulator. In a previous study, we discovered several small molecule Beclin 1 mimetics as autophagy inducers through high-throughput screening and structural optimization, in which 3-nitroacridine warrants further exploration. Here, a series of novel 3-nitroacridine derivatives were designed, synthesized, and their pharmaceutical activities and mechanism of action were investigated against gastric cancer cell lines. As a result, compounds 3, 4, and 9 displayed potent cytotoxicity and induced autophagy in MGC-803 and SGC-7901 gastric cancer cells. Besides, compounds 3 and 9 also inhibited the migration of SGC-7901 cells. The development of 3-nitroacridine analogues as autophagy inducers is not only likely to be a potential strategy for cancer therapy, but it will also facilitate a better understanding of the complicated roles of autophagy in normal physiology and pathophysiology.

Graphical abstract: Identification of novel 3-nitroacridines as autophagy inducers in gastric cancer cells

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Publication details

The article was received on 10 Jan 2017, accepted on 12 Apr 2017 and first published on 12 Apr 2017


Article type: Paper
DOI: 10.1039/C7NJ00119C
Citation: New J. Chem., 2017,41, 4087-4095
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    Identification of novel 3-nitroacridines as autophagy inducers in gastric cancer cells

    J. Yu, X. Zhao, N. Zhang, C. You, G. Yao, J. Zhu, L. Xu and B. Sun, New J. Chem., 2017, 41, 4087
    DOI: 10.1039/C7NJ00119C

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