Synthesis and biological evaluation of quinoline analogues of flavones as potential anticancer agents and tubulin polymerization inhibitors

被引：91

作者：

Shobeiri, Nikta ^{[1
,2
]}

Rashedi, Maryam ^{[1
,2
]}

Mosaffa, Fatemeh ^{[1
]}

Zarghi, Afshin ^{[3
]}

Ghandadi, Morteza ^{[1
]}

Ghasemi, Ali ^{[4
]}

Ghodsi, Razieh ^{[1
,2
]}

机构：

[1] Mashhad Univ Med Sci, Biotechnol Res Ctr, Mashhad, Iran

[2] Mashhad Univ Med Sci, Sch Pharm, Dept Med Chem, Mashhad, Iran

[3] Shahid Beheshti Univ Med Sci, Dept Pharmaceut Chem, Sch Pharm, Tehran, Iran

[4] Mashhad Univ Med Sci, Dept Pediat Oncol Hematol, Sch Med, Mashhad, Iran

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 114卷

关键词：

Quinolines; Tubulin polymerization; Anticancer activity; Molecular docking; Resistant cancer cells; DESIGN; DERIVATIVES;

D O I：

10.1016/j.ejmech.2016.02.069

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new series of 2-aryl-trimethoxyquinoline analogues was designed and synthesized as tubulin inhibitors using methoxylated flavones as the lead compounds. The cytotoxic activity of the synthesized compounds was evaluated against four human cancer cell lines including MCF-7, MCF-7/MX, A-2780, and A-2780/RCIS. All the alcoholic derivatives (6a-6e) showed significant cytotoxic activity with IC50 in the range of 7:98-60 mu M. The flow cytometry analysis of the four human cancer cell lines treated with 6e and 5b showed that 6e induced cell cycle arrest at G2/M phase and apoptosis as well. The effect of quinolines on tubulin polymerization was also evaluated. Compound 6e that demonstrated the best antiproliferative activity in the series was identified as the most potent inhibitor of tubulin polymerization as well. Molecular docking studies of 6e into the colchicine-binding site of tubulin displayed possible mode of interaction between this compound and tubulin. (C) 2016 Elsevier Masson SAS. All rights reserved.

引用

页码：14 / 23

页数：10

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