Structure-based design of new poly (ADP-ribose) polymerase (PARP-1) inhibitors

被引：12

作者：

Chadha, Navriti ^{[1
]}

Jaggi, Ameteshar Singh ^{[2
]}

Silakari, Om ^{[1
]}

机构：

[1] Punjabi Univ, Dept Pharmaceut Sci & Drug Res, MML, Patiala 147002, Punjab, India

[2] Punjabi Univ, Dept Pharmaceut Sci & Drug Res, Patiala 147002, Punjab, India

来源：

MOLECULAR DIVERSITY | 2017年 / 21卷 / 03期

关键词：

Structure-based drug design; Docking; Thiazolidine-2,4-dione; Indole; Molecular modeling; PARP; DERIVATIVES; DOMAIN;

D O I：

10.1007/s11030-017-9754-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Poly (ADP-ribose) polymerase (PARP-1) is a well-established nuclear protein with prominent role in signaling and DNA repair. Various clinical candidates have been identified with the role in PARP-1 inhibition. Based on the pharmacophoric features identified from previous studies and molecular docking interactions, thiazolidine-2,4-dione derivatives have been evaluated for their PARP inhibitory activity. From an in vitro assay, 5-((1-(4-isopropylbenzyl)-1H- indol-3-yl) methylene) thiazolidine-2,4-dione (16) was identified as a potent inhibitor having low micromolar inhibitory activity (IC50 = 0.74 +/- 0.25 mu M). Thus, a structure-based design approach utilized in the present study helped to identify thiazolidine-2,4-dione as a novel scaffold against PARP-1 for potential development of potent anticancer therapeutics.

引用

页码：655 / 660

页数：6

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