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DNA Interstrand Cross‐Linking Efficiency and Cytotoxic Activity of Novel Cadmium( II )–Thiocarbodiazone Complexes
Author(s) -
Pérez José M.,
Cerrillo Virginia,
Matesanz Ana I.,
Millán Juan M.,
Navarro Paloma,
Alonso Carlos,
Souza Pilar
Publication year - 2001
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/1439-7633(20010202)2:2<119::aid-cbic119>3.0.co;2-5
Subject(s) - cisplatin , cytotoxic t cell , cytotoxicity , chemistry , dna , pbr322 , glutathione , dna damage , plasmid , stereochemistry , in vitro , biochemistry , biology , genetics , enzyme , chemotherapy
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.