Anticancer Platinum(IV) Prodrugs Containing Monoaminophosphonate Ester as a Targeting Group Inhibit Matrix Metalloproteinases and Reverse Multidrug Resistance

作者：Huang, Xiaochao; Huang, Rizhen; Gou, Shaohua^*; Wang, Zhimei; Wang, Hengshan^*

来源：Bioconjugate Chemistry, 2017, 28(4): 1305-1323.

DOI：10.1021/acs.bioconjchem.7b00117

• ANTITUMOR-ACTIVITY
• IN-VITRO
• UNIQUE MODE
• COMPLEXES
• CISPLATIN
• DERIVATIVES
• MOIETY
• INSIGHTS
• DELIVERY
• PHOSPHONATES

A novel class of platinum(W) complexes comprising a monoamino-phosphonate 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(W) 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.

• 出版日期2017-4
• 单位东南大学; 广西师范大学