Mono- and di-bromo platinum(IV) prodrugs via oxidative bromination: synthesis, characterization, and cytotoxicity.

Abstract

Platinum(IV)-based anticancer prodrugs have attracted much attention due to their relative inertness under physiological conditions, being activated inside cells, and their capacity for functionalization with a variety of small-molecule or macromolecule moieties. Novel asymmetric platinum(IV) compounds synthesized through expedient and unique methods are desired. Here we utilize N-bromosuccinimide (NBS) and carry out oxidative bromination on platinum(II) drugs, namely cisplatin, carboplatin, and oxaliplatin, to obtain asymmetric and mono-bromo platinum(IV) prodrugs. Different solvents are used to obtain various compounds, and the compounds are further functionalized. Di-bromo compounds are also obtained through NBS-directed oxidative bromination in ethanol. The crystal structures of representative compounds are discussed, and the reduction potentials of some compounds are examined. A cytotoxicity test shows that the mono- and di-bromo platinum(IV) compounds are active against human ovarian cancer cells. Our study enriches the family of asymmetric platinum(IV) prodrugs and provides with a convenient strategy to obtain brominated platinum(IV) complexes.

• Authors: Zoufeng Xu, Zhigang Wang, Shek-Man Yiu, Guangyu Zhu
• Journal: Dalton transactions (Cambridge, England : 2003) (Dalton Trans) Vol. 44 Issue 46 Pg. 19918-26 (Dec 14 2015) ISSN: 1477-9234 [Electronic] England
• PMID: 26514681 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Organoplatinum Compounds
• Prodrugs
• Oxaliplatin
• Platinum
• Carboplatin
• Bromosuccinimide
• Cisplatin

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Bromosuccinimide (chemistry)
• Carboplatin (chemistry, pharmacology)
• Cell Line, Tumor
• Cisplatin (analogs & derivatives, chemistry, pharmacology)
• Female
• Halogenation
• Humans
• Models, Molecular
• Organoplatinum Compounds (chemistry, pharmacology)
• Ovarian Neoplasms (drug therapy)
• Ovary (drug effects)
• Oxaliplatin
• Oxidation-Reduction
• Platinum (chemistry, pharmacology)
• Prodrugs (chemistry, pharmacology)