Lysine-specific demethylase 1 (LSD1), which has been reported to be overexpressed in several human cancers, has recently emerged as an attractive therapeutic target for treating cancer. To date, almost all the developed LSD1 inhibitors are chemo-synthesized molecules, while α-mangostin is first characterized as xanthone-based natural inhibitor in the current study with IC₅₀ values of 2.81 ± 0.44 μM. Bioactivity study and docking analysis indicated that α-mangostin could inhibit MDA-MB-231 cells migration and evasion through inhibit intracellular LSD1 activity. These findings provides new molecular skeleton for LSD1 inhibitor study and should encourage further modification of α-mangostin to produce more potent LSD1 inhibitors with potential anticancer activity.

据报道，赖氨酸特异性脱甲基酶1（LSD1）在几种人类癌症中均过表达，最近已成为治疗癌症的有吸引力的治疗靶标。迄今为止，几乎所有已开发的LSD1抑制剂都是化学合成的分子，而α-Mangostin在本研究中首次被表征为基于黄酮的天然抑制剂，IC ₅₀值为2.81±0.44μM。生物活性研究和对接分析表明，α-Mangostin可通过抑制细胞内LSD1活性来抑制MDA-MB-231细胞的迁移和逃避。这些发现为LSD1抑制剂的研究提供了新的分子骨架，并应鼓励进一步修饰α-mangostin以产生具有潜在抗癌活性的更有效的LSD1抑制剂。