Synthesis, characterization and antiproliferative studies of the enantiomers of cis-[(1,2-camphordiamine)dichloro]platinum(II) complexes
| Autor: | Virtudes Moreno, Consuelo Batalla, Carlos Farnós, Francisco J. Bernal, Ángel M. Montaña, María J. Prieto, Julia Lorenzo, M.T. Alegre, Francesc X. Avilés, Juan M. Mesas |
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| Rok vydání: | 2008 |
| Předmět: |
Circular dichroism
Organoplatinum Compounds Stereochemistry Clinical Biochemistry Pharmaceutical Science chemistry.chemical_element Antineoplastic Agents HL-60 Cells Diamines Biochemistry Chemical synthesis Inhibitory Concentration 50 chemistry.chemical_compound Drug Discovery Humans Molecular Biology Cell Proliferation Organic Chemistry Stereoisomerism Biological activity DNA Ethylenediamines Camphor Enantiopure drug chemistry Molecular Medicine Agarose Enantiomer Platinum |
| Zdroj: | Bioorganic & Medicinal Chemistry. 16:1721-1737 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2007.11.021 |
| Popis: | The platinum(II) complex cis -[(1 S ,2 R ,3 S )-1,7,7-trimethylbicyclo[2.2.1]heptane-2,3-diamine]dichloroplatinum(II) ( 1 ) and its enantiomer ( 2 ) have been synthesized and physically and spectroscopically characterized. To obtain the enantiopure complexes the chiral pool approach was applied. The synthetic pathway has four steps, starting from (±)-diphenylethylenediamine (DPEDA) ( 3 ) and the natural products (1 S )-camphorquinone or (1 R )-camphorquinone to obtain enantiomers 1 and 2 , respectively. The interaction of the Pt(II) complexes with DNA was studied by several techniques: circular dichroism, electrophoresis on agarose gel and atomic force microscopy (AFM). These studies showed differences in the degree of interaction between both enantiomers and DNA (calf thymus DNA and plasmid pBR322 DNA). The cytotoxicity of enantiomers 1 and 2 against the HL-60 cell line was studied by in vitro tests of antiproliferative activity, incubating during both 24 h and 72 h. An important difference of activity was found between both enantiomers regarding the IC 50 data at 24 h of incubation. Thus, complex 1 showed to be much more active than its enantiomer 2 . |
| Databáze: | OpenAIRE |
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