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A series of novel 1,2,3-triazole-dithiocarbamate-urea hybrids were designed, synthesized and their antiproliferative activities against four selected human cancer cell lines were evaluated. The results showed that a number of the hybrids exhibited potent activity in selected human cancer cell lines. Among them, compounds 27 and 34 showed broad spectrum anticancer activity with IC50 values ranging from 1.62 to 20.84 μM and 0.76 to 13.55 μM, respectively. Interestingly, compounds 27 and 34, being very potent against MGC-803 cells, exhibited no significant cytotoxicity against normal human embryonic kidney cells at up to 55 μM and 70 μM, respectively. Evidences of cell cycle arrest and apoptosis induction were obtained for the most effective compounds 27 and 34 by means of flow cytometry and microscopic techniques., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Lysine specific demethylase 1 (LSD1) plays an essential role in maintaining a balanced methylation status at histone tails. Overexpression of LSD1 has been involved in the development of a variety of human diseases, including cancers. Herein, on the basis of our previously developed LSD1 inhibitors, two series of new [1,2,3]triazolo[4,5- d ]pyrimidine derivatives incorporating (thio)urea moiety were designed and evaluated for their LSD1 inhibitory abilities, leading to a novel chemical class of LSD1 inhibitors. Among them, compound 31 was found to moderately inhibit LSD1 activity, as well as increase the expression of H3K4me2 at the cellular level. This compound also showed good selectivity against MAO-A/-B, and a panel of kinases such as CDK and BTK. Besides, the MTT assay suggested that the selected compounds could inhibit the proliferation of LSD1-overexpressed cancer cells. Although this class of compounds only showed moderate anti-LSD1 activity in the micromolar range, this work presents a novel chemotype of LSD1 inhibitors with good enzyme selectivity as well as cellular LSD1 inhibitory activity, and could provide a useful template for the development of more potent LSD1 inhibitors for cancer treatment. Image 1 • The [1,2,3]triazolo[4,5- d ]pyrimidin-7-one/(thio)urea hybrids represent a new chemical class of LSD1 inhibitors. • Compound 31 had moderate inhibitory activity against LSD1. • Compound 31 had good enzyme selectivity. • The selected LSD1 inhibitors had antiproliferative activity against LSD1-overexpressed tumor cells. [ABSTRACT FROM AUTHOR]