化学
顺铂
细胞毒性
细胞凋亡
基质金属蛋白酶
奥沙利铂
前药
细胞培养
癌细胞
药理学
癌症研究
生物化学
癌症
体外
化疗
内科学
医学
结直肠癌
生物
遗传学
作者
Xiaochao Huang,Ri-Zhen Huang,Shaohua Gou,Zhimei Wang,Heng‐Shan Wang
标识
DOI:10.1021/acs.bioconjchem.7b00117
摘要
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.
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