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IJC-A Vol.50A(03-04) [March-April 2011] >


Title: Copper(I) complexes of modified nucleobases and vitamin B3 as potential chemotherapeutic agents: In vitro and in vivo studies
Authors: Sanghamitra, N J M
Adwankar, M K
Juvekar, A S
Khurajjam, V
Wycliff, C
Samuelson, A G
Keywords: Bioinorganic chemistry
Metallodrugs
Copper
Antitumor activity
Thiopyrimidine
Nicotinamide
Cytotoxicity
Lipophilicity
Issue Date: Mar-2011
Publisher: NISCAIR-CSIR, India
Abstract: Three new complexes of Cu(I) have been synthesized using ancillary ligands like thiopyrimidine (tp) a modified nucleobase, and nicotinamide (nic) 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] (1) and [Cu(PPh3)2(tp)]ClO4 (2) have in vitro cytotoxicity comparable to cisplatin. Complex [Cu(nic)3PPh3]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 105 M and completely cleaves super-coiled DNA at a concentration of 400 M, whereas complexes (1) and (2) do not bind DNA and do not show any cleavage even at 1200 M. Thus, complex (3) may exhibit cytotoxicity via DNA cleavage whereas the mechanism of cytotoxicity of (1) and (2) probably involves a different pathway.
Page(s): 465-473
CC License:  CC Attribution-Noncommercial-No Derivative Works 2.5 India
ISSN: 0975-0975(Online); 0376-4710(Print)
Source:IJC-A Vol.50A(03-04) [March-April 2011]

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