当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Platinated benzonaphthyridone is a stronger inhibitor of poly(ADP-ribose) polymerase-1 and a more potent anticancer agent than is the parent inhibitor.

Platinated benzonaphthyridone is a stronger inhibitor of poly(ADP-ribose) polymerase-1 and a more potent anticancer agent than is the parent inhibitor.

Abstract：

:Inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1) have shown to be promising in clinical trials against cancer and other diseases, and lots of efforts have been put into the development of organic compounds as more potent PARP-1 inhibitors. Here we describe a strategy to conveniently obtain metal-based PARP-1 inhibitors with enhanced biological activities by conjugating platinum moiety with an original inhibitor, e.g., benzonaphthyridone. Based on the structure-activity relationship analysis of PARP-1 inhibitors, three platinated PARP-1 inhibitors were designed, and the complexes were synthesized and characterized. Complex 3 presented significantly enhanced cytotoxicity against a panel of human cancer cells and a 10-fold increased inhibitory effect against recombinant PARP-1 compared with the original PARP-1 inhibitor. Complex 3 was as cytotoxic as cisplatin and its spectrum of anticancer activity was identical to that of cisplatin. The complex was able to enter into cancer cells efficiently, bind to DNA well, and block cell cycle at G₂/M phase, indicating that complex 3 is an effective anticancer agent with a distinct mechanism of action. Our study implies that the conjugation of platinum with PARP-1 inhibitors could be a valid strategy to obtain more potent anticancer agents with improved biological activities.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Wang B,Qian H,Yiu SM,Sun J,Zhu G

doi

10.1016/j.ejmech.2013.10.062

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

366-73

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(13)00713-7

journal_volume

71

pub_type

杂志文章

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