Discovery of Novel Sulphonamide Hybrids That Inhibit LSD1 Against Bladder Cancer Cells

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2022 Mar 30

PMID 35350943

Authors

Jia Liu

Xingwang Zhu

Liu Yu

Minghuan Mao

Affiliations

Soon will be listed here.

Abstract

A series of sulphonamide hybrids were designed, synthesised, and identified as potential lysine-specific demethylase 1 (LSD1) inhibitors. Bladder cancer cell lines were cultured to evaluate the antiproliferative activity. Inhibitory evaluation of sulphonamide hybrids against LSD1 were performed. sulphonamide derivative exhibited the antiproliferative activity against HTB5, HTB3, HT1376, and HTB1 cells with IC values of 1.87, 0.18, 0.09, and 0.93 μM, respectively. Compound as a selective and reversible LSD1 inhibitor could inhibit LSD1 with the IC value of 60 nM. It effectively inhibited LSD1 by increasing the expression levels of H3K4me1, H3K4me2, and H3K9me2 in HT1376 cells. To the best of our knowledge, this was the first report which showed that sulphonamide-quinoline-dithiocarbamate hybrids potently inhibited LSD1 in bladder cancer cells. Our studies give the potential application of the sulphonamide-based scaffold for developing LSD1 inhibitors to treat bladder cancer.

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