Highly potent Platinum(IV) complexes with multiple-bond ligands targeting mitochondria to overcome cisplatin resistance.

Abstract

The efficacy and resistance of cisplatin-based compounds are very intractable problems at present. This study reports a series of platinum(IV) compounds containing multiple-bond ligands, which exhibited better tumor cell inhibitory activity and antiproliferative and anti-metastasis activities than cisplatin. The meta-substituted compounds 2 and 5 were particularly excellent. Further research showed that compounds 2 and 5 possessed appropriate reduction potential and performed significantly better than cisplatin in cellular uptake, reactive oxygen species response, the up-regulation of apoptosis and DNA lesion-related genes, and drug-resistant cell activity. The title compounds exhibited better antitumor potential and fewer side effects than cisplatin in vivo. Multiple-bond ligands were introduced into cisplatin to form the title compounds in this study, which not only enhanced their absorption and overcame drug resistance but also demonstrated the potential to target mitochondria and inhibit the detoxification of tumor cells.

• Authors: Bo Fang, Xue Chen, Xingui Zhou, Xindan Hu, Yan Luo, Zhigang Xu, Cheng-He Zhou, Jiang-Ping Meng, Zhong-Zhu Chen, Chunsheng Hu
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 250 Pg. 115235 (Mar 15 2023) ISSN: 1768-3254 [Electronic] France
• PMID: 36863226 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier Masson SAS. All rights reserved.

Chemical References

• Cisplatin
• Platinum
• Antineoplastic Agents
• Organoplatinum Compounds

Topics

• Cisplatin (pharmacology)
• Platinum (pharmacology, chemistry)
• Antineoplastic Agents (chemistry)
• Drug Resistance, Neoplasm
• Organoplatinum Compounds (chemistry)
• Mitochondria
• Cell Line, Tumor