| Water-soluble platinum(II) complexes of diamine chelating ligands bearing amino-acid type substituents: the effect of the linked amino acid and the diamine chelate ring size on antitumor activity, and interactions with 5'-GMP and DNA. | |
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MedLine Citation:
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PMID: 15522419 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Six new Pt(II) complexes are described having the general formula PtCl(2)(LL), in which LL is a chelating diamine ligand bearing an amino acid as substituent. The amino acids chosen are l-alanine and its methyl ester, and l-phenylalanine. The compounds have been characterized using analytical and spectroscopic methods. The influence on the biological properties of the size of the chelate ring and the structure of the amino acid substituent has been studied. The effect of the presence of a carboxylic or carboxylate group on the amino acid C-terminus has also been determined. It is demonstrated by circular dichroism (CD) that the effect on the secondary structure of DNA induced by the six complexes differ from each other. In all cases, the interaction takes place at the N7 position of the purine bases, as shown by NMR monitoring. The general behavior of these platinum complexes, with one exception, is to uncoil the DNA from the B form to the C form. The interactions with 5'-GMP and DNA have been compared with their expected antitumour activity. The complexes with l-alanine and l-phenylalanine exhibit cytotoxic activity in HeLa and HL-60 cell lines, in a dose- and time-dependent manner. No cytotoxic activity of the methyl ester derivatives have been determined because of their low solubility in aqueous solution. |
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Authors:
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Silvia Moradell; Julia Lorenzo; Ana Rovira; Steven van Zutphen; Francesc X Avilés; Virtudes Moreno; Rafael de Llorens; M Angeles Martinez; Jan Reedijk; Antoni Llobet |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of inorganic biochemistry Volume: 98 ISSN: 0162-0134 ISO Abbreviation: J. Inorg. Biochem. Publication Date: 2004 Nov |
Date Detail:
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Created Date: 2004-11-03 Completed Date: 2005-10-11 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7905788 Medline TA: J Inorg Biochem Country: United States |
Other Details:
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Languages: eng Pagination: 1933-46 Citation Subset: IM |
Affiliation:
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Departament de Química, Area de Química Inorgànica, Facultat de Ciències, Universitat de Girona, Av. Montilivi s/n, 17071 Girona, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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5'-Guanylic Acid
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chemistry* Amino Acids DNA / chemistry* Diamines Magnetic Resonance Spectroscopy Models, Molecular Molecular Conformation Organoplatinum Compounds / chemical synthesis, chemistry* Solubility Structure-Activity Relationship Water |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids; 0/Diamines; 0/Organoplatinum Compounds; 7732-18-5/Water; 85-32-5/5'-Guanylic Acid; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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