2. Academic Validation
  3. Design, synthesis, and antitumor activity of matrine aminophosphonate derivatives as potent mcl-1 inhibitors

Design, synthesis, and antitumor activity of matrine aminophosphonate derivatives as potent mcl-1 inhibitors

  • Bioorg Chem. 2026 Feb:169:109449. doi: 10.1016/j.bioorg.2025.109449.
Xiaoqun Zhou 1,  Mingjun Zhu 1,  Caina Jiang 1,  Xianli Ma 1,  Fangyao Li 2
Affiliations

Affiliations

  • 1 Guangxi Key Laboratory of Drug Discovery and Optimization, Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability Evaluation, Key Laboratory of Medical Biotechnology and Translational Medicine, School of Pharmacy, Guilin Medical University, Guilin, Guangxi 541199, PR China.
  • 2 Guangxi Key Laboratory of Drug Discovery and Optimization, Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability Evaluation, Key Laboratory of Medical Biotechnology and Translational Medicine, School of Pharmacy, Guilin Medical University, Guilin, Guangxi 541199, PR China. Electronic address: [email protected].
PMID: 41494370 DOI: 10.1016/j.bioorg.2025.109449
Abstract

A series of novel matrine aminophosphonate derivatives were designed and synthesized to explore more efficacious and less toxic Mcl-1 inhibitors, following the principle of combination and hybridization. The representative compound, 9 k, exhibited more potent cytotoxicity against human cervical Cancer cells compared to the positive control 5-FU. A molecular docking study was also conducted to understand the interactions of 9 k with the Mcl-1 protein. Mechanistic studies revealed that compound 9 k could induce Apoptosis in Hela cells, accompanied by changes in chromatin morphology, an elevation of intracellular ROS levels, and the dissipation of MMP. Notably, in vivo studies indicated that 9 k inhibited tumor growth in a Hela xenograft model. In summary, this study suggests that compound 9 k represents a potent and selective Mcl-1 Inhibitor for the treatment of human cervical Cancer.

Keywords

Aminophosphonate; Cell apoptosis; Matrine; Mcl-1 inhibitors.

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