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  3. Synthesis, optimization and antitumor activity evaluation of sulfonyl benzoyl hydrazide derivatives as novel human LSD1 inhibitors

Synthesis, optimization and antitumor activity evaluation of sulfonyl benzoyl hydrazide derivatives as novel human LSD1 inhibitors

  • Bioorg Med Chem Lett. 2024 Oct 9:114:129982. doi: 10.1016/j.bmcl.2024.129982.
Wei Ai 1,  Zeping Zuo 2
Affiliations

Affiliations

  • 1 Laboratory of Anaesthesiology & Critical Care Medicine, Department of Anesthesiology, State Key Laboratory of Biotherapy and Cancer Center and Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
  • 2 Laboratory of Anaesthesiology & Critical Care Medicine, Department of Anesthesiology, State Key Laboratory of Biotherapy and Cancer Center and Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Laboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu, PR China. Electronic address: Zepingzuo@163.com.
PMID: 39384076 DOI: 10.1016/j.bmcl.2024.129982
Abstract

A new set of compounds known as sulfonyl benzoyl hydrazide derivatives were synthesized and tested using cellular assays. Through systematic optimization starting from general structure S-1, compound 10e emerged as highly promising. It exhibited potent inhibitory activity with an IC50 value of 0.8 nM and possessed moderate clogP. Compounds 10e significantly inhibited solid tumor cells proliferation. Additionally, 10e induced Apoptosis and arrested the cell cycle. Furthermore, in vivo studies using an HCT116 xenograft model showed substantial growth inhibition of tumors, accompanied by a favorable safety profile. These findings underscored compound 10e as a novel LSD1 inhibitor with robust efficacy both in vitro and in vivo, establishing it as a promising lead compound for further Anticancer drug development.

Keywords

Benzoyl hydrazide derivatives; LSD1; Structure–activity relationship.

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