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Title: Copper(I) complexes of modified nucleobases and vitamin B3 as potential chemotherapeutic agents: <i style="">In vitro</i> and <i style="">in vivo</i> studies
Authors: Sanghamitra, N J M
Adwankar, M K
Juvekar, A S
Khurajjam, V
Wycliff, C
Samuelson, A G
Keywords: Bioinorganic chemistry
Antitumor activity
Issue Date: Mar-2011
Publisher: NISCAIR-CSIR, India
Abstract: Three new complexes of Cu(I) have been synthesized using ancillary ligands like thiopyrimidine (<b style="">tp</b>) a modified nucleobase, and nicotinamide (<b style="">nic</b>) or vitamin B3, and characterized by spectroscopy and X-ray crystallography. <i style="">In vitro</i> cytotoxicity studies of the complexes on various human cancer cell lines such as Colo295, H226, HOP62, K562, MCF7 and T24 show that [Cu(PPh<sub>3</sub>)<sub>2</sub>(<b style="">tp</b>)Cl] <b style="">(1)</b> and [Cu(PPh<sub>3</sub>)<sub>2</sub>(<b style="">tp</b>)]ClO<sub>4 </sub><b style="">(2)</b> have <i style="">in vitro</i> cytotoxicity comparable to cisplatin. Complex [Cu(<b style="">nic</b>)<sub>3</sub>PPh<sub>3</sub>]ClO<sub>4 </sub><b style="">(3)</b> is non-toxic and increases the life span by about 55 % in spontaneous breast tumor model. DNA binding and cleavage studies show that complex <b style="">(3)</b> binds to calf thymus DNA with an apparent binding constant of 5.9 x 10<sup>5 </sup><i style="">M</i> and completely cleaves super-coiled DNA at a concentration of 400 <img src='/image/spc_char/micro.gif' border=0> <i style="">M</i>, whereas complexes <b style="">(1) </b>and <b style="">(2)</b> do not bind DNA and do not show any cleavage even at 1200 <img src='/image/spc_char/micro.gif' border=0> <i style="">M</i>. Thus, complex <b style="">(3)</b> may exhibit cytotoxicity via DNA cleavage whereas the mechanism of cytotoxicity of <b style="">(1)</b> and <b style="">(2)</b> probably involves a different pathway.
Description: 465-473
ISSN: 0975-0975(Online); 0376-4710(Print)
Appears in Collections:IJC-A Vol.50A(03-04) [March-April 2011]

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