ArticleRSC advances2025
Synthesis and anticancer activity of Pt(iv) prodrugs containing 3-bromopyruvic acid as an axial ligand.
Article in RSC advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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9 authors.
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Abstract
A Pt(iv) prodrug of oxaliplatin incorporating the glycolysis inhibitor 3-bromopyruvic acid, BrPt3, was designed and investigated. The prodrug is reduced in the presence of ascorbic acid, releasing its active Pt(ii) species and axial ligand. In cytotoxicity studies, BrPt3 exhibited stronger anticancer activity than oxaliplatin against all tested cancer cell lines, particularly in oxaliplatin-resistant A549/OXP cells. By effectively inhibiting glycolysis, BrPt3 induced greater DNA damage in tumor cells. It arrested the cell cycle at the G0/G1 phase, leading to increased apoptosis and significantly reduced cell invasiveness. BrPt3 resulted in higher platinum accumulation in the genomic DNA of MKN28, HCT116, and HT29 cells, though no significant difference in DNA-platinum adduct formation was observed in A549/OXP cells. Compared to oxaliplatin, BrPt3 more effectively impaired the glycolytic capacity of tumor cells, as evidenced by significantly reduced levels of pyruvate, lactate, ATP, and HK2 enzyme expression.
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