Identification of novel potent and non-toxic anticancer, anti-angiogenic and antimetastatic rhenium complexes against colorectal carcinoma

被引：53

作者：

Delasoie, Joachim ^{[1
]}

Pavic, Aleksandar ^{[2
]}

Voutier, Noemie ^{[1
]}

Vojnovic, Sandra ^{[2
]}

Crochet, Aurelien ^{[1
]}

Nikodinovic-Runic, Jasmina ^{[2
]}

Zobi, Fabio ^{[1
]}

机构：

[1] Fribourg Univ, Dept Chem, Chemin Musee 9, CH-1700 Fribourg, Switzerland

[2] Univ Belgrade, Inst Mol Genet & Genet Engn, Vojvode Stepe 444a, Belgrade 11042152, Serbia

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2020年 / 204卷

基金：

瑞士国家科学基金会;

关键词：

Colorectal carcinoma; Rhenium; Zebrafish; Xenograft; Angiogenesis; Antimetastatic; CANCER-CELL METABOLISM; IN-VIVO; TRICARBONYL COMPLEXES; PHOTOPHYSICAL PROPERTIES; IRIDIUM(III) COMPLEXES; PLATINUM(II) COMPLEXES; CARBONYL-COMPLEXES; CYTOTOXIC ACTIVITY; MASS-SPECTROMETRY; SOLUTION BEHAVIOR;

D O I：

10.1016/j.ejmech.2020.112583

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Combination therapy targeting both tumor growth and vascularization is considered to be a cornerstone for colorectal carcinomas (CRC) treatment. However, the major obstacles of most clinical anticancer drugs are their weak selective activity towards cancer cells and inherent inner organs toxicity, accompanied with fast drug resistance development. In our effort to discover novel selective and non-toxic agents effective against CRC, we designed, synthesized and characterized a series of rhenium(I) tricarbonyl-based complexes with increased lipophilicity. Two of these novel compounds were discovered to possess remarkable anticancer, anti-angiogenic and antimetastatic activity in vivo (zebrafish-human HCT-116 xenograft model), being effective at very low doses (1-3 mu M). At doses as high as 250 mu M the complexes did not provoke toxicity issues encountered in clinical anticancer drugs (cardio-, hepato-, and myelotoxicity). In vivo assays showed that the two compounds exceed the anti-tumor and anti-angiogenic activity of clinical drugs cisplatin and sunitinib malate, and display a large therapeutic window. (C) 2020 Elsevier Masson SAS. All rights reserved.

引用

页数：18

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