Cytotoxic copper(II) complex of tripyridoquinoxaline with DNA hydrolase activity

A monomeric copper(II) complex, [Cu(tPq)(2)(H2O)(2)](ClO4)(2), (tpq = tripyridoquinoxaline), has been synthesized and characterized spectroscopically. This complex has been found to bind DNA intercalatively and the DNA binding constant, K-b, for this complex has been determined from absorption measurements and was found to be (5.7 +/- 0.3) x 10(3) M-1. This complex successfully promotes hydrolytic cleavage of plasmid DNA. producing single and double DNA strand breaks in the absence of any added cofactor. The amount of conversion of the supercoiled form of plasmid to the nicked circular form depends on the concentration of the copper complex as well as the duration of the incubation of the complex with DNA. The rate of conversion of SC to NC has been determined to be 2.65 x 10(-4) s(-1) at pH 7.2 in the presence of 80 mu M of the complex. This complex has also been shown to be cytotoxic towards A549 lung adenocarcinoma cells. This complex has been shown to bring about apoptosis of the cancerous A549 cell line. (C) 2011 Elsevier Ltd. All rights reserved.