Discovery of tranylcypromine analogs with an acylhydrazone substituent as LSD1 inactivators: Design,synthesis and their biological evaluation |
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| Authors: | Kai Sun Jia-Di Peng Feng-Zhi Suo Ting Zhang Yun-Dong Fu Yi-Chao Zheng Hong-Min Liu |
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| Affiliation: | 1. Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China;2. Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, PR China;3. Key Laboratory of Henan Province for Drug Quality and Evaluation, PR China;4. School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China;5. National Center for International Research of Micro-nano Molding Technology & Key Laboratory for Micro Molding Technology of Henan Province, Zhengzhou University, Zhengzhou 450001, PR China |
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| Abstract: | Lysine specific demethylase 1 (LSD1), the first identified histone demethylase, plays an important role in epigenetic regulation of gene activation and repression, has been reported to be up-regulated and involved in numbers of solid malignant tumors. In this study, we identified a series of phenylalanyl hydrazones based LSD1 inhibitors, and the most potent one, compound 4q, can inactivate LSD1 with IC50?=?91.83?nM. In cellular level, compound 4q can induce the accumulation of CD86 as well as H3K4me2, and inhibit gastric cancer cell proliferation by inactivating LSD1. Our findings indicated that compound 4q may serve as a potential leading compound to target LSD1 overexpressed gastric cancer. |
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| Keywords: | LSD1 Inhibitor Phenylalanyl hydrazones Tranylcypromine |
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