Document Detail

Design, synthesis and SAR studies of novel 1,2-bis(aminomethyl)cyclohexane platinum(II) complexes with cytotoxic activity. Studies of interaction with DNA of iodinated seven-membered 1,4-diaminoplatinocycles.
MedLine Citation:
PMID:  25305632     Owner:  NLM     Status:  Publisher    
A selected library of nine novel platinum(II) complexes having differently functionalized 1,2-bis(aminomethyl)cyclohexane carrier ligands with a 1,4-diamino framework and iodides as labile ligands have been synthesized and evaluated in vitro for their tumor cell growth inhibitory activity, in front of one pair of human carcinoma cell lines A2780 and A2780cisR. These cell lines were chosen based on studying all the known main mechanisms of resistance of cisplatin. A2780cisR cells are resistant through a combination of reduced drug transport enhanced DNA repair/tolerance and elevated glutathione (GSH) levels with respect to the parental A2780 cells. Most platinum complexes evaluated showed a very low resistant factor, up to 16 times lower than that of cisplatin, which indicates their ability to overcome the cisplatin resistance in ovarian cancer A2780cisR cells. Structure-activity studies have been performed in order to know the influence of the several organic functionalities (CC double bond, free OH group, MeO group, etc.) and the stereochemistry on the cytotoxic activity. Moreover, studies of interaction with DNA of these complexes were performed via three techniques: circular dichroism (CD), electrophoresis on agarose gel (EF) and atomic force microscopy (AFM) in order to evaluate the modifications of secondary and tertiary structure of DNA, induced by platinum complexes. These studies allowed us to correlate the IC50 values of complexes and the intensity of interaction to DNA, the main target for these compounds.
Marina Gay; Angel M Montaña; Consuelo Batalla; Juan M Mesas; María-Teresa Alegre
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-28
Journal Detail:
Title:  Journal of inorganic biochemistry     Volume:  142C     ISSN:  1873-3344     ISO Abbreviation:  J. Inorg. Biochem.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-10-11     Completed Date:  -     Revised Date:  2014-10-12    
Medline Journal Info:
Nlm Unique ID:  7905788     Medline TA:  J Inorg Biochem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  15-27     Citation Subset:  -    
Copyright Information:
Copyright © 2014 Elsevier Inc. All rights reserved.
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