DNA Interstrand Cross-Linking Efficiency and Cytotoxic Activity of Novel Cadmium(II)-Thiocarbodiazone Complexes

Abstract

We have prepared mono- and binuclear complexes of Zn(II) and Cd(II) with bis(2-pyridyl aldehyde) thiocarbodiazone (H(2)L(1)) and bis(methyl 3-pyridyl ketone) thiocarbodiazone (H(2)L(2)). Cytotoxicity data against the ovarian tumor cell line A2780cisR (acquired resistance to cisplatin) indicate that the mononuclear complex Cd/H(2)L(2) (1) and the binuclear complex Cd(2)/H(2)L(1) (4) are able to circumvent cisplatin resistance and that their cytotoxic activity does not substantially vary after depletion of intracellular levels of glutathione. Moreover, DNA binding studies show that complexes 1 and 4 have higher efficiency than cisplatin at forming DNA interstrand cross-links in both naked pBR322 plasmid and A2780cisR cellular DNA. Interestingly, the thiocarbodiazone ligands alone do not show the biological properties of complexes 1 and 4. Altogether these results suggest that DNA interstrand cross-link formation by compounds 1 and 4 might be related with their cytotoxic activity in cisplatin-resistant cells. We think that compounds 1 and 4 may represent a novel structural lead for the development of cadmium cytotoxic agents capable of improving antitumor activity in cisplatin-resistant tumors.

Novel cyclopalladated and coordination palladium and platinum complexes derived from α-diphenyl ethanedione bis(thiosemicarbazones): Structural studies and cytotoxic activity against human A2780 and A2780cisR carcinoma cell lines

“…In recent years there has been an emergence of new structural types of compounds often with promising activity [4][5][6][7]. For instance, the substitution of the chlorido ligands by other anionic ligands could lead to the new active complexes.…”

Novel cyclopalladated and coordination palladium and platinum complexes derived from α-diphenyl ethanedione bis(thiosemicarbazones): Structural studies and cytotoxic activity against human A2780 and A2780cisR carcinoma cell lines

“…In recent years there has been an emergence of new structural types of compounds often with promising activity [4][5][6][7]. For instance, the substitution of the chlorido ligands by other anionic ligands could lead to the new active complexes.…”

Effect of Manganese Chloride and of Cotreatment with Cadmium Chloride on the In Vitro Proliferative, Motile, and Invasive Behavior of MDA-MB231 Breast Cancer Cells

“…This might be achieved by cotargeting cellular sites and components, and reprogramming the molecular and biochemical pathways of MnCl 2 -stimulated TNBC cells. The inhibitory activity of Cd-containing compounds on viability and growth of normal and neoplastic cells and the mitigatory effect provided by Zn-containing molecules have been reported in the literature [46,47,48]. Taking the limited treatment options against TNBC into account, the specific anticancer modulatory property of CdCl 2 towards MDA-MB231 cells here reported looks promising and deserves a more detailed biological characterization of the involved intracellular targets aimed to the possible molecular modeling of specific antineoplastic agents with improved effectiveness towards the inhibition of the spreading of malignant breast cancer.…”

Palladium(II) and platinum(II) bis(thiosemicarbazone) complexes of the 2,6-diacetylpyridine series with high cytotoxic activity in cisplatin resistant A2780cisR tumor cells and reduced toxicity

“…These disadvantages have driven the development of improved 50 platinum-based anticancer drugs different from the traditional cisplatin 51 structure and which could probably have different DNA-binding modes 52 as well as exhibit different biological profiles [6][7][8][9][10].…”

Novel cyclopalladated and coordination palladium and platinum complexes derived from α-diphenyl ethanedione bis(thiosemicarbazones): Structural studies and cytotoxic activity against human A2780 and A2780cisR carcinoma cell lines

“…In recent years there has been an emergence of new structural types of compounds often with promising activity [4][5][6][7]. For instance, the substitution of the chlorido ligands by other anionic ligands could lead to the new active complexes.…”

Effect of Manganese Chloride and of Cotreatment with Cadmium Chloride on the In Vitro Proliferative, Motile, and Invasive Behavior of MDA-MB231 Breast Cancer Cells

“…This might be achieved by cotargeting cellular sites and components, and reprogramming the molecular and biochemical pathways of MnCl 2 -stimulated TNBC cells. The inhibitory activity of Cd-containing compounds on viability and growth of normal and neoplastic cells and the mitigatory effect provided by Zn-containing molecules have been reported in the literature [46,47,48]. Taking the limited treatment options against TNBC into account, the specific anticancer modulatory property of CdCl 2 towards MDA-MB231 cells here reported looks promising and deserves a more detailed biological characterization of the involved intracellular targets aimed to the possible molecular modeling of specific antineoplastic agents with improved effectiveness towards the inhibition of the spreading of malignant breast cancer.…”

Palladium(II) and platinum(II) bis(thiosemicarbazone) complexes of the 2,6-diacetylpyridine series with high cytotoxic activity in cisplatin resistant A2780cisR tumor cells and reduced toxicity

“…These disadvantages have driven the development of improved 50 platinum-based anticancer drugs different from the traditional cisplatin 51 structure and which could probably have different DNA-binding modes 52 as well as exhibit different biological profiles [6][7][8][9][10].…”

Novel cyclopalladated and coordination palladium and platinum complexes derived from α-diphenyl ethanedione bis(thiosemicarbazones): Structural studies and cytotoxic activity against human A2780 and A2780cisR carcinoma cell lines

“…In recent years there has been an emergence of new structural types of compounds often with promising activity [4][5][6][7]. For instance, the substitution of the chlorido ligands by other anionic ligands could lead to the new active complexes.…”

Effect of Manganese Chloride and of Cotreatment with Cadmium Chloride on the In Vitro Proliferative, Motile, and Invasive Behavior of MDA-MB231 Breast Cancer Cells

“…This might be achieved by cotargeting cellular sites and components, and reprogramming the molecular and biochemical pathways of MnCl 2 -stimulated TNBC cells. The inhibitory activity of Cd-containing compounds on viability and growth of normal and neoplastic cells and the mitigatory effect provided by Zn-containing molecules have been reported in the literature [46,47,48]. Taking the limited treatment options against TNBC into account, the specific anticancer modulatory property of CdCl 2 towards MDA-MB231 cells here reported looks promising and deserves a more detailed biological characterization of the involved intracellular targets aimed to the possible molecular modeling of specific antineoplastic agents with improved effectiveness towards the inhibition of the spreading of malignant breast cancer.…”

Palladium(II) and platinum(II) bis(thiosemicarbazone) complexes of the 2,6-diacetylpyridine series with high cytotoxic activity in cisplatin resistant A2780cisR tumor cells and reduced toxicity

“…These disadvantages have driven the development of improved 50 platinum-based anticancer drugs different from the traditional cisplatin 51 structure and which could probably have different DNA-binding modes 52 as well as exhibit different biological profiles [6][7][8][9][10].…”