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-(2-pyridyl)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)H(2) L complex with CT-DNA was determined (K(B) = 1.8 × 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)H(2) L complex. The Cd(II)H(2) L 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.

Cadmium Modifies the Cell Cycle and Apoptotic Profiles of Human Breast Cancer Cells Treated with 5-Fluorouracil

“…In cancer cells, Cd was found to decrease the proportion of cells in the G2/M phase, and induce apoptosis, resulting in a substantial decrease in the number of viable cells [33,34]. Several studies have revealed that the cellular damage induced by 5-FU involves a loss or accumulation of cells in the S phase, G2/M block, and G1/S arrest [35].…”

Synthesis, characterization, cytotoxic activity and DNA binding properties of the novel dinuclear cobalt(III) complex with the condensation product of 2-acetylpyridine and malonic acid dihydrazide

“…The value lies in the range characteristic for binding by intercalation [37], but the steric clashes with DNA exterior caused by the second ligand bound to Co(III) dictates its DNA-binding mode to be surface binding to minor groove. The value differs for one order of magnitude from previously investigated Cd(II) complex with H 2 L which was characterized as minor groove binder [11]. High value of the binding constant for a minor groove binder might be a consequence of the helicoidal geometry of the complex (Fig.…”

“…The heptacoordinated binuclear Cd(II) complex with H 2 L showed very good cytotoxic activity already in the low micromolar range [8]. The activity was, at least in part, a consequence of strong binding to DNA [11]. These promising results prompted us to evaluate if other analogous metal complexes exhibit similar behavior.…”

“…The absorbance titrations were performed at a fixed concentration of [Co 2 L 2 ](NO 3 ) 2 ·2H 2 O· 0.5C 2 H 5 OH complex and varying the concentration of double stranded CT-DNA. For an individual experiment, each DNA solution (1,2,3,4,5,6,8,9,10,11,12,13,14 and 15 μL of CT-DNA stock solution) was pipetted into a separate vial, to which 10 μL of a stock solution of compound were added and the volume adjusted to 1 mL with water. Reaction mixtures were incubated at 37°C for 2 h with occasional vortexing.…”

Synthesis, Spectral and Solid State Characterization of a New Bioactive Hydrazine Bridged Cyclic Diphosphonium Compound

“…A major interest of our research group is devoted to metal complexes of polydentate dihydrazone ligands [1][2][3][4][5], mainly because some of these complexes display substantial cytotoxic activity [2][3][4]. While searching for new ligands we have focused our attention on those that combine both hard and soft donor atoms [6][7][8][9][10][11], in particular the heterofunctionalised phosphines, where the phosphorus is the soft donor, and the hard donor is either an oxygen or nitrogen atom.…”