In Vitro and in Vivo Anticancer Activity of Copper Bis(thiosemicarbazone) Complexes

Palanimuthu, Duraippandi and Shinde, Sridevi Vijay and Somasundaram, Kumaravel and Samuelson, Ashoka G (2013) In Vitro and in Vivo Anticancer Activity of Copper Bis(thiosemicarbazone) Complexes. In: JOURNAL OF MEDICINAL CHEMISTRY, 56 (3). pp. 722-734.

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Abstract

Neutral and cationic copper bis(thiosemicarbazone) complexes bearing methyl, phenyl, and hydrogen, on the diketo-backbone of the ligand have been synthesized. All of them were characterized by spectroscopic methods and in three cases by X-ray crystallography. In vitro cytotoxicity studies revealed that they are cytotoxic unlike the corresponding zinc complexes. Copper complexes Cu(GTSC) and Cu(GTSCHCl) derived from glyoxal-bis(4-methyl-4-phenyl-3-thiosemicarbazone) (GTSCH(2)) are the most cytotoxic complexes against various human cancer cell lines, with a potency similar to that of the anticancer drug adriamycin and up to 1000 fold higher than that of the corresponding zinc complex. Tritiated thymidine incorporation assay revealed that Cu(GTSC) and Cu(GTSCHCl) inhibit DNA synthesis substantially. Cell cycle analyses showed that Cu(GTSC) and Cu(GTSCHCl) induce apoptosis in HCT116 cells. The Cu(GTSCHCl) complex caused distinct DNA cleavage and Topo II alpha inhibition unlike that for Cu(GTSC). In vivo administration of Cu(GTSC) significantly inhibits tumor growth in HCT116 xenografts in nude mice.

Item Type:	Journal Article
Publication:	JOURNAL OF MEDICINAL CHEMISTRY
Publisher:	AMER CHEMICAL SOC
Additional Information:	Copyright for this article belongs to AMER CHEMICAL SOC, USA
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited:	28 Mar 2013 12:06
Last Modified:	28 Mar 2013 12:06
URI:	http://eprints.iisc.ac.in/id/eprint/46247

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