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Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
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Novel Cytotoxic Pt(IV) Compounds with Improved Safety Profiles.

Anastasia A Antonets1, Ksenia M Voroshilkina1, Ilya A Shutkov1

  • 1Department of Chemistry, M.V. Lomonosov Moscow State University, Leninskie Gory 1/3, Moscow 119991, Russia.

International Journal of Molecular Sciences
|February 27, 2026
PubMed
Summary

New platinum(IV) complexes with vitamin E analogs show enhanced antioxidant and anticancer activity. These novel compounds exhibit improved efficacy against cancer cells while reducing toxicity to normal cells, offering a promising strategy for cancer therapy.

Keywords:
anticancer activityantioxidant activitycisplatinconjugationcytotoxicityoxaliplatinplatinum (IV)

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Area of Science:

  • Medicinal Chemistry
  • Nanotechnology
  • Biochemistry

Background:

  • Platinum(II)-based drugs like cisplatin are vital cancer treatments but face limitations including side effects and resistance.
  • Platinum(IV) complexes are being investigated as prodrugs for targeted cancer therapy.
  • Synthetic vitamin E analogs offer potential for improved safety profiles in drug development.

Purpose of the Study:

  • To synthesize and evaluate novel platinum(IV) complexes conjugated with synthetic vitamin E analogs.
  • To assess the antioxidant properties and in vitro cytotoxicity of these new platinum(IV) complexes.
  • To compare the efficacy and safety of the novel complexes against cisplatin in cancer and normal cell lines.

Main Methods:

  • Synthesis of platinum(IV) complexes incorporating phenolic ligands.
  • Evaluation of antioxidant activity using DPPH, CUPRAC assays, and lipid peroxidation inhibition.
  • Assessment of in vitro cytotoxicity via MTT assay on various cancer and normal cell lines.

Main Results:

  • The synthesized platinum(IV) complexes demonstrated significant antioxidant properties due to the phenolic ligands.
  • Novel complexes exhibited enhanced cytotoxic activity against cancer cell lines compared to cisplatin.
  • Reduced toxicity was observed in normal fibroblast cells treated with the novel complexes in vitro.

Conclusions:

  • Conjugating antioxidant ligands to platinum(IV) scaffolds effectively modulates redox processes and biological activity.
  • This design strategy holds potential for developing more effective platinum-based cancer therapies with improved safety.
  • The novel platinum(IV) complexes represent a promising advancement in the development of next-generation anticancer agents.