期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 204, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2020.112583
关键词
Colorectal carcinoma; Rhenium; Zebrafish; Xenograft; Angiogenesis; Antimetastatic
资金
- Swiss National Science Foundation [PP00P2_170589]
- University of Fribourg
- Institute of Molecular Genetics and Genetic Engineering from the University of Belgrade (Ministry of Education, Science and Technological Development of the Republic of Serbia) [173048]
- Swiss National Science Foundation (SNF) [PP00P2_170589] Funding Source: Swiss National Science Foundation (SNF)
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.
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