Benzothienoquinazolinones as new multi-target scaffolds: Dual inhibition of human Topoisomerase I and tubulin polymerization

被引：42

作者：

Ceramella, Jessica ^{[1
]}

Caruso, Anna ^{[1
]}

Occhiuzzi, Maria Antonietta ^{[1
]}

Lacopetta, Domenico ^{[1
]}

Barbarossa, Alexia ^{[1
]}

Rizzuti, Bruno ^{[2
]}

Dallemagne, Patrick ^{[3
]}

Rault, Sylvain ^{[3
]}

El-Kashef, Hussein ^{[4
]}

Saturnino, Carmela ^{[5
]}

Grande, Fedora ^{[1
]}

Sinicropi, Maria Stefania ^{[1
]}

机构：

[1] Univ Calabria, Dept Pharm Hlth & Nutrit Sci, I-87036 Arcavacata Di Rende, CS, Italy

[2] Univ Calabria, CNR, Licryl UOS, Cosenza & CEMIE Cal,NANOTEC,Dept Phys, Via P Bucci, I-87036 Arcavacata Di Rende, CS, Italy

[3] Normandie Univ, CERMN, UNICAEN, F-14000 Caen, France

[4] Assiut Univ, Fac Sci, Chem Dept, Assiut 71516, Egypt

[5] Univ Basilicata, Dept Sci, Potenza, Italy

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2019年 / 181卷

关键词：

Tubulin; Cytoskeleton; Breast cancer; Docking study; Benzothienoquinazolinones; BIOLOGICAL EVALUATION; DERIVATIVES; MICROTUBULE; ELLIPTICINE; EFFICIENT; CELLS; 1,4-DIMETHYLCARBAZOLES; MECHANISM; ANTITUMOR; DOCKING;

D O I：

10.1016/j.ejmech.2019.111583

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

3-(Alkyl(diallcyl)amino)benzothieno[2,3-f]quinazolin-1(211)-ones (4-9) have been designed using Ellipticine structure as a model, replacing the carbazole core and the pyridine ring with a dibenzothiophene and a pyrimidine moiety, respectively. New benzothienoquinazolinones (4-9) have been synthesized by a simple one-pot reaction employing 3-aminodibenzothiophene as starting material. The benzothienoquinazolinones obtained (4-9), were evaluated for their anticancer activity against two breast cancer cell lines, MDA-MB-231 and MCF-7. The results revealed that compounds 4 and 7 presented a good antitumor activity toward the triple negative MDA-MB-231, without cytotoxicity against non-tumoral cells. Furthermore, the compounds 4 and 7 can be considered important molecular multi-target tools for their dual inhibition of different cellular proteins, i.e. Tubulin and human Topoisomerase I, involved in relevant cellular processes, as predicted by in silico studies and demonstrated by in vitro assays (for compound 4). (C) 2019 Elsevier Masson SAS. All rights reserved.

引用

页数：9

共 54 条

[41] N-thioalkylcarbazoles derivatives as new anti-proliferative agents: synthesis, characterisation and molecular mechanism evaluation [J].