Identification of human telomerase inhibitors having the core of N-acyl-4,5-dihydropyrazole with anticancer effects

被引：6

作者：

Xiao, Xuan ^{[1
]}

Ni, Yong ^{[1
]}

Jia, Ying-Ming ^{[2
]}

Zheng, Min ^{[1
]}

Xu, Han-Fei ^{[1
]}

Xu, Jun ^{[3
,4
]}

Liao, Chenzhong ^{[1
]}

机构：

[1] Hefei Univ Technol, Sch Med Engn, Hefei 230009, Peoples R China

[2] Anhui Univ Technol, Sch Chem & Chem Engn, Maanshan 243002, Peoples R China

[3] Sun Yat Sen Univ, Res Ctr Drug Discovery, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China

[4] Sun Yat Sen Univ, Inst Human Virol, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 06期

关键词：

Telomerase; Telomerase inhibitor; Dihydropyrazole; Anticancer; Molecular modeling; 5-FLUOROURACIL DERIVATIVES; REVERSE-TRANSCRIPTASE; MOLECULAR DOCKING; ETHANONE; DESIGN; ASSAY; DNA;

D O I：

10.1016/j.bmcl.2016.02.025

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Eight human telomerase inhibitors (5a-5h) having the core of N-acyl-4,5-dihydropyrazole with anticancer effects were identified in this study. Biological results revealed that a few compounds had potent anticancer activities against three common tumor cell lines (SGC-7901, HepG2 and MGC-803). Among them, compound 5c, with a molecular weight of only 272.2 Da, had antiproliferative activities against SGC-7901 and MGC-803 with EC50 values of 2.06 +/- 0.17 and 2.89 +/- 0.62 mu M, respectively, better than 5-Fluorouracil. Compound 5c inhibited the enzyme of telomerase with an IC50 value of 1.86 +/- 0.51 mu M, surpassing the control compound, ethidium bromide. Modeling study showed that this compound can reside in the binding pocket of the telomerase/TNA: DNA hairpin complex. When the moiety of N-acyl was changed to N-sulfonyl, the gotten compounds (8a-8i) had deteriorative activities against both these three cancer cell lines and the enzyme of telomerase. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：1508 / 1511

页数：4