2. Academic Validation
  3. Design, synthesis and biological evaluation of novel guanidine-containing matrine derivatives as Topo I/II dual target inhibitors

Design, synthesis and biological evaluation of novel guanidine-containing matrine derivatives as Topo I/II dual target inhibitors

  • Eur J Med Chem. 2026 Sep 5:313:118884. doi: 10.1016/j.ejmech.2026.118884.
Shihao Li 1,  Yu Zhu 2,  Yonghui Wang 3,  Xuan Liu 3,  Zheng Xu 3,  Qinghai Dong 3,  Shuobing Wang 3,  Linlin Cui 3,  Chunyan Lv 3,  Zhihua Xing 3,  Yiru Wang 3,  Guanghuan Shen 4,  Guoyu Li 5
Affiliations

Affiliations

  • 1 College of Pharmacy, Harbin University of Commerce, Harbin, 150076, PR China. Electronic address: 15964170810@163.com.
  • 2 College of Pharmacy, Harbin University of Commerce, Harbin, 150076, PR China. Electronic address: 13882180549@163.com.
  • 3 College of Pharmacy, Harbin University of Commerce, Harbin, 150076, PR China.
  • 4 College of Pharmacy, Harbin University of Commerce, Harbin, 150076, PR China. Electronic address: shengh@hrbcu.edu.cn.
  • 5 College of Pharmacy, Harbin University of Commerce, Harbin, 150076, PR China. Electronic address: liguoyu@hrbcu.edu.cn.
PMID: 42054768 DOI: 10.1016/j.ejmech.2026.118884
Abstract

Topoisomerase inhibitors are a key focus in the development of antitumor agents. In this work, using matrine as a lead compound, a series of novel derivatives were designed and synthesized as potential dual inhibitors of Topoisomerase I and II (Topo I/II). Among these compounds, A6 and A10 exhibited significant cytotoxicity against MCF-7 cells, with IC50 values of 0.6 μM and 0.7 μM, respectively, comparable to those of the positive controls (CPT, VP-16). Given their superior cytotoxicity and dual Topo I/II inhibitory activity, these two compounds were selected for further pharmacological evaluation. Mechanistic investigations demonstrated that A6 and A10 effectively suppressed the proliferation, invasion, and migration of MCF-7 cells in vitro by inducing DNA damage and activating the mitochondrial apoptotic pathway. Collectively, these findings underscore the potential of A6 and A10 as novel dual Topo I/II inhibitors for Cancer therapy.

Keywords

Antitumor activity; Apoptosis; Dual Topo I/II inhibitors; Matrine derivatives.

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