Novel Tranylcypromine/Hydroxylcinnamic Acid Hybrids as Lysine-Specific Demethylase 1 Inhibitors with Potent Antitumor Activity

作者：Han, Yan^*; Wu, Chunlei; Lv, Haifeng; Liu, Na; Deng, Huaying

来源：CHEMICAL & PHARMACEUTICAL BULLETIN, 2015, 63(11): 882-889.

DOI：10.1248/cpb.c15-00476

• synthesis
• lysine-specific demethylase
• inhibitory activity
• tranylcypromine
• hydroxylcinnamic acid
• antitumor agent

Novel tranylcypromine/hydroxylcinnamic acid hybrids 15a, b, and 19a-1 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 191 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 191 selectively inhibited cancer cell but not nontumor colon cell proliferation in vitro. In addition, compound 191 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.

• 出版日期2015-11
• 单位温州医科大学