Synthesis, anticancer, and cytotoxic activities of some mononuclear Ru(II) compounds.

Abstract

The synthesis and characterization of ruthenium compounds (Ru1-Ru12) of the type [Ru(S)(2)(K)], (where S=1,10-phenanthroline/2,2'-bipyridine and K=itsz, MeO-btsz, 4-Cl-btsz, 2-Cl-btsz, 2-F-btsz, hfc and itsz=isatin-3-thiosemicarbazone, MeO-btsz=1-(4'-methoxy-benzyl)-thiosemicarbazone, hfc=2-{[3-chloro-4-fluoro-phenylimino]methyl}phenol, 4-Cl-btsz=1-(4'-chlorobenzyl)-thiosemicarbazone, 2-Cl-btsz=1-(2'-chloro benzyl)-thiosemicarbazone, 2-F-btsz=1-(2'-fluorobenzyl)-thiosemicarbazone) are described. These ligands form bidentate octahedral ruthenium compounds. The title compounds were subjected to in vivo anticancer activity against a transplantable murine tumor cell line Ehrlich's Ascites Carcinoma (EAC) and in vitro cytotoxic activity against human cancer cell line Molt 4/C8, CEM and murine tumor cell line L1210. Ruthenium compounds (Ru1-Ru12) showed promising biological activity especially in decreasing tumor volume and viable ascites cell counts. Treatment with these compounds prolonged the life span of mice bearing EAC tumor by 10-43%. In vitro evaluation of these ruthenium compounds revealed cytotoxic activity from 0.24 to 27 microM against Molt 4/C8, 0.27 to 48 microM against CEM, and 0.94 to 248 microM against L1210. Their ligands alone failed to show cytotoxic activity at the concentrations tested (68-405 microM).

• Authors: Subhas S Karki, Sreekanth Thota, Satyanarayana Y Darj, Jan Balzarini, Erik De Clercq
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 15 Issue 21 Pg. 6632-41 (Nov 01 2007) ISSN: 0968-0896 [Print] England
• PMID: 17765549 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Ligands
• Organometallic Compounds
• Ruthenium

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Carcinoma, Ehrlich Tumor
• Cell Line, Tumor
• Humans
• Ligands
• Mice
• Mice, Inbred Strains
• Organometallic Compounds (chemical synthesis, chemistry, pharmacology)
• Ruthenium (chemistry)
• Xenograft Model Antitumor Assays