Discovery of the Next-Generation Platinum-Based Anticancer Agents for Combating Oxaliplatin-Induced Drug Resistance.

J Med Chem

School of Pharmaceutical Science and Technology, Institute of Molecular Plus, Frontiers Science Center for Synthetic Biology (Ministry of Education of China), Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, P. R.

Published: June 2024


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Article Abstract

Oxaliplatin-based chemotherapy has proven to be one of the most effective treatments for advanced or metastatic colorectal cancer. However, increasing clinical resistance to oxaliplatin poses unprecedented challenges for both patients and clinicians. Despite extensive efforts to combat this issue, to date, no new molecules have been discovered that can successfully replace oxaliplatin. With the aim of developing a new generation of Pt(II)-based anticancer agents in response to the challenges of oxaliplatin-induced drug resistance, we performed a systematic screening of new Pt(II)-complexes with a quantitative structure-activity relationship (QSAR) study based on their antiresistance activity against oxaliplatin-resistant colon cancer cells. The results revealed that both the structure and chirality of the chelating ligand had a significant impact on the antiresistance properties of the Pt(II)-complexes. Our study culminated in the identification of chiral -binaphthyldiamine-ligated Pt(II)-malonatoglycoconjugates that can completely counteract oxaliplatin resistance with excellent and potency.

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http://dx.doi.org/10.1021/acs.jmedchem.4c00366DOI Listing

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