Benzimidazoles as new scaffold of sirtuin inhibitors: Green synthesis, in vitro studies, molecular docking analysis and evaluation of their anti-cancer properties

被引：57

作者：

Yoon, Yeong Keng ^{[1
]}

Ali, Mohamed Ashraf ^{[1
,2
,3
]}

Wei, Ang Chee ^{[1
]}

Shirazi, Amir Nasrolahi

Parang, Keykavous ^{[4
]}

Choon, Tan Soo ^{[1
]}

机构：

[1] Univ Sains Malaysia, Inst Res Mol Med, Minden 11800, Penang, Malaysia

[2] Alwar Pharm Coll, Dept Med Chem, Alwar 301030, Rajasthan, India

[3] Sunrise Univ, Dept Med Chem, Alwar 301030, Rajasthan, India

[4] Univ Rhode Isl, Coll Pharm, Dept Biomed & Pharmaceut Sci, Kingston, RI 02881 USA

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 83卷

关键词：

Sirtuin; Benzimidazole; Anti-proliferative; Green chemistry synthesis; 2-SUBSTITUTED BENZIMIDAZOLES; ONE-POT; DEACETYLASES; DISCOVERY; TOXICITY; FAMILY; SIR2;

D O I：

10.1016/j.ejmech.2014.06.060

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Two series of novel benzimidazole derivatives were designed, synthesized and evaluated for their SIRT1 and SIRT2 inhibitory activity. Among the newly synthesized compounds, compound 4j displayed the best inhibitory activity for SIRT1 (IC50 = 54.21 mu M) as well as for SIRT2 (IC50 = 26.85 mu M). Cell proliferation assay showed that compound 4j possessed good antitumor activity against three different types of cancer cells derived from colon (HCT-116), breast (MDA-MB-468) and blood-leukemia (CCRF-CEM) with cell viability of 40.0%, 53.2% and 27.2% respectively at 50 mu M. Docking analysis of representative compound 4j into SIRT2 indicated that the interaction with receptor was primarily due to hydrogen bonding and pi-pi stacking interactions. (C) 2014 Elsevier Masson SAS. All rights reserved.

引用

页码：448 / 454

页数：7

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