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Lysine-specific demethylase 1 (LSD1), demethylase against mono- and di - methylated histone3 lysine 4, has emerged as a promising target in oncology. More specifically, it has been demonstrated as a key promoter in acute myeloid leukemia (AML), and several LSD1 inhibitors have already entered into clinical trials for the treatment of AML. In this paper, a series of new indole derivatives were designed and synthesized based on a lead compound obtained by a high-throughput screening with our in-house compound library. Among the synthetic compounds, 9e was characterized as a potent LSD1 inhibitor with an IC 50 of 1.230 μM and can inhibit the proliferation of THP-1 cells effectively. And most importantly, this is the first irreversible LSD1 inhibitor that is not derived from monoamine oxidase inhibitors. Hence, the discovery of 9e may serve as a proof of concept work for AML treatment. Image 1 • Compound 9e was designed and synthesized based on a lead compound obtained from our in-house compound library. • Compound 9e inhibits LSD1 (IC50 = 1.230 μM) and shows good anti-proliferation activity in THP-1 cells. • Compound 9e can significantly increase the expression of CD86 and induce differentiation of THP-1 cells. • Compound 9e is the first irreversible LSD1 inhibitor that is not derived from monoamine oxidase inhibitors. [ABSTRACT FROM AUTHOR]

• It is the first time to characterize Sanggenon O as an anticancer compound. • Sanggenon O induced the expressions of cytoplasmic vacuoles and autophagic markers in NSCLC A549 cell line. • Sanggenon O suppressed autophagic flux in NSCLC A549 cell lines. • Sanggenon O induces cytoprotective autophagy in NSCLC A549 cell lines. Sanggenon O (SO) is a Diels-Alder type adduct extracted from Morus alba , which has been used for its anti-inflammatory action in the Oriental medicine. However, whether it has regulatory effect on human cancer cell proliferation and what the underlying mechanism remains unknown. Here, we found that SO could significantly inhibit the growth and proliferation of A549 cells and induce its pro-apoptotic action through a caspase-dependent pathway. It could also impair the mitochondria which can be reflected by mitochondrial membrane permeabilization. Besides, SQSTM1 up-regulation and autophagic flux measurement demonstrated that exposure to SO led to autophagosome accumulation, which plays a protective role in SO-treated cells. In addition, knocking down of LC3B increased SO triggered apoptotic cell rates. These results indicated that SO has great potential as a promising candidate combined with autophagy inhibitor for the treatment of NSCLC. In conclusion, our results identified a novel mechanism by which SO exerts potent anticancer activity. [ABSTRACT FROM AUTHOR]