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

Abstract

Dysregulated autophagy is involved in various human disorders including cancer. Autophagy-associated cell death pathway can be seen as a back-up cell death mechanism in cancer cells that are deficient in 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 process via binding to the BH3-only protein Beclin 1, an essential autophagy stimulator. In previous study, we have discovered several small molecule Beclin 1 mimetics as autophagy inducers through high-throughput screening and structure 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 pathway 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 effects of autophagy in normal physiology and pathophysiology.

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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, Accepted Manuscript
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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, Accepted Manuscript , DOI: 10.1039/C7NJ00119C

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