Synthesis and evaluation of the cytotoxic activity of Furanaphthoquinones tethered to 1H-1,2,3-triazoles in Caco-2, Calu-3, MDA-MB231 cells

被引：30

作者：

Costa, Dora C. S. ^{[1
]}

de Almeida, Gabriella Silva ^{[2
]}

Rabelo, Vitor Won-Held ^{[3
]}

Cabral, Lucio Mendes ^{[2
]}

Sathler, Plinio Cunha ^{[2
]}

Abreu, Paula Alvarez ^{[3
]}

Ferreira, Vitor Francisco ^{[4
]}

Rodrigues Pereira da Silva, Luiz Claudio ^{[2
]}

da Silva, Fernando De C. ^{[1
]}

机构：

[1] Univ Fed Fluminense, Inst Quim, Dept Quim Organ, Campus Valonguinho, BR-24020150 Niteroi, RJ, Brazil

[2] Univ Fed Rio de Janeiro, LabTIF, Fac Farm, BR-21941902 Rio De Janeiro, RJ, Brazil

[3] Univ Fed Rio de Janeiro, Lab Modelagem Mol & Pesquisa Ciencias Farmaceut L, NUPEM, Campus Macae, BR-27965045 Rio De Janeiro, RJ, Brazil

[4] Univ Fed Fluminense, Dept Tecnol Farmaceut, Fac Farm, BR-24241002 Niteroi, RJ, Brazil

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2018年 / 156卷

关键词：

Quinones; Triazole; Cancer; Anticancer agents; Molecular modelling; Topoisomerase; IN-VITRO CYTOTOXICITY; TRYPANOSOMA-CRUZI; MOLLUSCICIDAL ACTIVITY; STRUCTURAL BASIS; BETA-LAPACHONE; ATPASE DOMAIN; TOPOISOMERASE; DERIVATIVES; DOCKING; NAPHTHOQUINONES;

D O I：

10.1016/j.ejmech.2018.07.018

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Naphthoquinones and 1,2,3-triazoles are structural pharmacophore that is known to impart several cancer cells. This work shows a synthetic methodology to obtain hybrid molecules involving naphthoquinone and triazol scaffold as multiple ligands. A simple and efficient synthetic route was used to prepare a series of sixteen compounds being eight 2-(1-aryl-1H-1,2,3-triazol-4-yl)-2,3-dihydronaphtho[1,2 b]furan-4,5-diones and eight 2-(1-aryl-1H-1,2,3-triazol-4-yl)-2,3- dihydronaphtho[2,3-b]furan-4,9-diones. These compounds were tested in MDA-MB231, Caco-2 and Calu-3 human cancer cells, and among them 7a was the most selective compound on Caco-2 cells, the most sensitized cell line in this study. In silico study suggest that the blockage of topoisomerase I and II alpha may be one of the mechanisms of action responsible for the cytotoxic effect of 7a in Caco-2 cells. (C) 2018 Elsevier Masson SAS. All rights reserved.

引用

页码：524 / 533

页数：10

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