title: 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.affiliation: Department of Biology and Chemistry, City University of Hong Kong, Kowloon Tong, Hong Kong SAR, China. guangzhu@cityu.edu.hk and City University of Hong Kong Shenzhen Research Institute, Shenzhen, P. R. China.
authors.forename: Zoufeng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, Kowloon Tong, Hong Kong SAR, China. guangzhu@cityu.edu.hk and City University of Hong Kong Shenzhen Research Institute, Shenzhen, P. R. China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, Kowloon Tong, Hong Kong SAR, China. guangzhu@cityu.edu.hk.
authors.forename: Shek-Man
authors.initials: SM
authors.lastname: Yiu
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, Kowloon Tong, Hong Kong SAR, China. guangzhu@cityu.edu.hk and City University of Hong Kong Shenzhen Research Institute, Shenzhen, P. R. China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001974:Bromosuccinimide / Q000737:chemistry*; D016190:Carboplatin / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D054879:Halogenation; D006801:Humans; D008958:Models, Molecular; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy; D010053:Ovary / Q000187:drug effects; D000077150:Oxaliplatin; D010084:Oxidation-Reduction; D010984:Platinum / Q000737:chemistry* / Q000494:pharmacology; D011355:Prodrugs / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011355:Prodrugs; D000077150:Oxaliplatin; D010984:Platinum; D016190:Carboplatin; D001974:Bromosuccinimide; D002945:Cisplatin