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Copper(I) complexes of modified nucleobases and vitamin B3 as potential chemotherapeutic agents: In vitro and in vivo studies

Sanghamitra, NJM and Adwankar, MK and Juvekar, AS and Khurajjam, V and Wycliff, C and Samuelson, AG (2011) Copper(I) complexes of modified nucleobases and vitamin B3 as potential chemotherapeutic agents: In vitro and in vivo studies. In: ndian Journal of Chemistry - Section A: Inorganic, Physical, Theoretical and Analytical Chemistry, 50 (3-4, S). pp. 465-473.

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Official URL: http://nopr.niscair.res.in/handle/123456789/11243

Abstract

Three new complexes of Cu(I) have been synthesized using ancillary ligands like thiopyrimidine (tp) a modified nucleobase, and nicotinamide (nie) or vitamin B3, and characterized by spectroscopy and X-ray crystallography. In vitro cytotoxicity studies of the complexes on various human cancer cell lines such as Colo295, H226, HOP62, K562, MCF7 and T24 show that Cu(PPh3)(2)(tp)Cl] and Cu(PPh3)(2)(tp)ClO4 (2) have in vitro cytotoxicity comparable to cisplatin. Complex Cu(nic)(3)PPh3]ClO4 (3) is non-toxic and increases the life span by about 55 % in spontaneous breast tumor model. DNA binding and cleavage studies show that complex (3) binds to calf thymus DNA with an apparent binding constant of 5.9 x 10(5)M and completely cleaves super-coiled DNA at a concentration of 400 mu M, whereas complexes (1) and (2) do not bind DNA and do not show any cleavage even at 1200 mu M. Thus, complex (3) may exhibit cytotoxicity Via DNA cleavage whereas the mechanism of cytotoxicity of (1) and (2) probably involves a different pathway.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to National Institute of Science Communication and Information Resources.
Keywords: Bioinorganic chemistry;Metallodrugs;Copper;Antitumor activity;Thiopyrimidine;Nicotinamide;Cytotoxicity; Lipophilicity
Department/Centre: Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited: 20 May 2011 06:56
Last Modified: 20 May 2011 06:56
URI: http://eprints.iisc.ernet.in/id/eprint/37685

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