title: Anticancer Platinum(IV) Prodrugs Containing Monoaminophosphonate Ester as a Targeting Group Inhibit Matrix Metalloproteinases and Reverse Multidrug Resistance.
abstract: A novel class of platinum(IV) complexes comprising a monoaminophosphonate ester moiety, which can not only act as a bone-targeting group but also inhibit matrix metalloproteinases (MMPs), were designed and synthesized. Biological assay of these compounds showed that they had potent antitumor activities against the tested cancer cell lines compared with cisplatin and oxaliplatin and indicated low cytotoxicity to human normal liver cells. Particularly, the platinum(IV) complexes were very sensitive to cisplatin resistant cancer cell lines. The corresponding structure-activity relationships were studied and discussed. Related mechanism study revealed that the typical complex 11 caused cell cycle arrest at S phase and induced apoptosis in Bel-7404 cells via a mitochondrial-dependent apoptosis pathway. Moreover, complex 11 had potent ability to inhibit the tumor growth in the NCI-H460 xenograft model comparable to cisplatin.
authors.forename: Xiaochao
authors.initials: X
authors.lastname: Huang
authors.forename: Rizhen
authors.initials: R
authors.lastname: Huang
authors.forename: Shaohua
authors.identifier: 0000-0003-0284-5480
authors.initials: S
authors.lastname: Gou
authors.forename: Zhimei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University , Guilin 541004, China.
authors.forename: Hengshan
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000494:pharmacology; D010984:Platinum / Q000627:therapeutic use*; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D009944:Organoplatinum Compounds; D011355:Prodrugs; D010984:Platinum; D020782:Matrix Metalloproteinases; D002945:Cisplatin