A Comparative Study of DNA Binding and Cell Cycle Phase Perturbation by the Dinuclear Complex of Cd(II) with the Condensation Product of 2-Acetylpyridine and Malonic Acid Dihydrazide N ',N ' 2-bis[(1E)-1-(2-pyridyl) ethylidene] propanedihydrazide

Abstract

Organometallic Cd(II) compounds have recently attracted attention for their anticancer activity. The interaction of the dinuclear complex of Cd(II) with the condensation product of 2-acetylpyridine and malonic acid dihydrazide, N',N'(2)-bis[(1E)-1-(2pyridyl) ethylidene] propanedihydrazide (Cd(II)H(2)L), with calf thymus DNA (CT-DNA) was monitored by blue shift in UV-vis spectra of the complex. The binding constant of Cd(II) H2L complex with CT-DNA was determined (K(B) = 1.8 x 10(4) M(-1)) and was indicative of minor groove binding. Agarose gel electrophoretic changes in mobility of supercoiled and circular forms of pBR322 and pUC18 plasmids in the presence of the complex suggest that conformational changes in the plasmids occur upon binding of the Cd(II) H2L complex. The Cd(II) H2L complex induced perturbation of the cell cycle phase distribution and an increase in the percentage of cells in the sub-G1 phase of human cervical cancer HeLa cell line and murine melanoma B16 cell line. Immunoblotting analysis showed the overexpression of Bcl-2 protein with the Cd(II)H(2)L complex.