PUBLICATION

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

Authors
Delasoie, J., Pavic, A., Voutier, N., Vojnovic, S., Crochet, A., Nikodinovic-Runic, J., Zobi, F.
ID
ZDB-PUB-200731-22
Date
2020
Source
European Journal of Medicinal Chemistry   204: 112583 (Journal)
Registered Authors
Keywords
Angiogenesis, Antimetastatic, Colorectal carcinoma, Rhenium, Xenograft, Zebrafish
MeSH Terms
  • Angiogenesis Inhibitors/chemistry
  • Angiogenesis Inhibitors/pharmacology
  • Animals
  • Antineoplastic Agents/chemistry
  • Antineoplastic Agents/pharmacology
  • Colorectal Neoplasms/pathology*
  • Coordination Complexes/chemistry*
  • Coordination Complexes/pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • HCT116 Cells
  • Humans
  • Neoplasm Metastasis
  • Rhenium/chemistry*
  • Xenograft Model Antitumor Assays
  • Zebrafish
PubMed
32731186 Full text @ Eur. J. Med. Chem.
Abstract
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 μM). At doses as high as 250 μM 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.
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