2. Academic Validation
  3. Discovery of a Novel Stilbene Derivative as a Microtubule Targeting Agent Capable of Inducing Cell Ferroptosis

Discovery of a Novel Stilbene Derivative as a Microtubule Targeting Agent Capable of Inducing Cell Ferroptosis

  • J Med Chem. 2022 Mar 24;65(6):4687-4708. doi: 10.1021/acs.jmedchem.1c01775.
Jingwei Zhou 1,  Yanqing Pang 2 3,  Weiwei Zhang 2,  Fen OuYang 2,  Haibiao Lin 2,  Xingshu Li 4,  Jun Yan 2 3
Affiliations

Affiliations

  • 1 Department of Quantum Chemistry, Wecomput Technology Company, Ltd. (Guangzhou), Room 807, Guangzhou International Financial Center, Zhujiang West Road, Tianhe District, Guangzhou 100085, P. R. China.
  • 2 Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510120, P. R. China.
  • 3 Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou 510120, P. R. China.
  • 4 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. China.
PMID: 35282680 DOI: 10.1021/acs.jmedchem.1c01775
Abstract

Microtubule targeting agents (MTAs) are used as clinically effective chemotherapies for Cancer treatment but might be limited by the acquired or intrinsic resistance of Cancer cells to Apoptosis. The vulnerability of therapy-resistant cancers to Ferroptosis provides an alternative way to overcome drug resistance. In this study, on the basis of the MTAs obtained in our previous studies, a series of MTAs were synthesized, and detailed structure-activity relationships were obtained through extensive molecular dynamics studies. Among them, a diphenylethene derivative, compound 33, displayed the most potent activity in vitro and in vivo, with IC50 values of 10-50 nM toward six Cancer cell lines and a 78.6% tumor growth inhibition in vivo. Interestingly, although it acted as the MTA, compound 33 triggered cell death mainly through cell Ferroptosis rather than Apoptosis, which might provide an alternative way to eradicate apoptosis-related drug resistance.

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