Novel Tranylcypromine/Hydroxylcinnamic Acid Hybrids as Lysine-Specific Demethylase 1 Inhibitors with Potent Antitumor Activity
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- Han Yan
- Department of Orthopedics, The First Affiliated Hospital, Wenzhou Medical University
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- Wu Chunlei
- Department of Orthopedics, The First Affiliated Hospital, Wenzhou Medical University
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- Lv Haifeng
- School of Pharmacy, Wenzhou Medical University
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- Liu Na
- Department of Traditional Medical Traumatology Orthopedics, Xi’an Honghui Hospital
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- Deng Huaying
- Department of Orthopedics, The First Affiliated Hospital, Wenzhou Medical University
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Abstract
Novel tranylcypromine/hydroxylcinnamic acid hybrids 15a, b, and 19a–l were designed and synthesized by connecting tranylcypromine with hydroxylcinnamic acid, and their biological activities were evaluated. The in vitro assay of their inhibitory activities against lysine-specific demethylase 1 (LSD1) showed that most of the target compounds displayed high potency with IC50 values ranging from submicromolar to single-digit micromolar levels. In particular, compound 19l had robust, selective LSD1 inhibitory activity, which was obviously higher than the inhibitory activity against homologues monoamine oxidase-A (MAO-A) and MAO-B, respectively. Furthermore, the most potent compound 19l selectively inhibited cancer cell but not nontumor colon cell proliferation in vitro. In addition, compound 19l also dose-dependently increased the expression of H3K4me2 at the cellular level. Our findings suggest that tranylcypromine/hydroxylcinnamic acid hybrids as LSD1 inhibitors may hold great promise as therapeutic agents for the treatment of human cancers.
Journal
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- Chemical and Pharmaceutical Bulletin
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Chemical and Pharmaceutical Bulletin 63 (11), 882-889, 2015
The Pharmaceutical Society of Japan
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Keywords
Details 詳細情報について
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- CRID
- 1390282679155301120
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- NII Article ID
- 130005105728
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- NII Book ID
- AA00602100
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- ISSN
- 13475223
- 00092363
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- NDL BIB ID
- 026829503
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- PubMed
- 26521853
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed