Biological assays and noncovalent interactions of pyridine-2-carbaldehyde thiosemicarbazonecopper(II) drugs with [poly(dA–dT)]2, [poly(dG–dC)]2, and calf thymus DNA
Autor: | Natalia Busto, Jorge F. Gaspar, R. Ruiz, José M. Leal, Rubén Gil-García, Marta González-Álvarez, Javier García-Tojal, Célia Martins, Saturnino Ibeas, Joaquín Borrás, Begoña García |
---|---|
Rok vydání: | 2010 |
Předmět: |
Thiosemicarbazones
Circular dichroism Stereochemistry Cleavage (embryo) Biochemistry Cell Line Ames test Inorganic Chemistry chemistry.chemical_compound Polydeoxyribonucleotides Poly dA-dT Bromide Organometallic Compounds Animals Non-covalent interactions 3-Mercaptopropionic Acid Semicarbazone chemistry.chemical_classification Aqueous solution Base Sequence Mutagenicity Tests Viscosity Spectrum Analysis DNA Breaks Temperature DNA Hydrogen-Ion Concentration Glutathione Dithiothreitol chemistry Cattle Oxidation-Reduction Copper |
Zdroj: | JBIC Journal of Biological Inorganic Chemistry. 15:515-532 |
ISSN: | 1432-1327 0949-8257 |
DOI: | 10.1007/s00775-009-0620-7 |
Popis: | The interaction of the Cu(II) drugs CuL(NO(3)) and CuL'(NO(3)) (HL is pyridine-2-carbaldehyde thiosemicarbazone and HL' is pyridine-2-carbaldehyde 4N-methylthiosemicarbazone, in water named [CuL](+) and [CuL'](+)) with [poly(dA-dT)](2), [poly(dG-dC)](2), and calf thymus (CT) DNA has been probed in aqueous solution at pH 6.0, I = 0.1 M, and T = 25 degrees C by absorbance, fluorescence, circular dichroism, and viscosity measurements. The results reveal that these drugs act as groove binders with [poly(dA-dT)](2), with a site size n = 6-7, whereas they act as external binders with [poly(dG-dC)](2) and/or CT-DNA, thus establishing overall electrostatic interaction with n = 1. The binding constants with [CuL'](+) were slightly larger than with [CuL](+). The title compounds display some cleavage activity in the presence of thiols, bringing about the rupture of the DNA strands by the reactive oxygen species formed by reoxidation of Cu(I) to Cu(II); this feature was not observed in the absence of thiols. Mutagenic assays performed both in the presence and in the absence of S9 mix, probed by the Ames test on TA 98, TA 100, and TA 102, were negative. Weak genotoxic activity was detected for [CuL](+) and [CuL'](+), with a significative dose-response effect for [CuL'](+), which was shown to be more cytotoxic in the Ames test and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation assays. Methylation of the terminal NH(2) group enhances the antiproliferative activity of the pyridine-2-carbaldehyde thiosemicarbazones. |
Databáze: | OpenAIRE |
Externí odkaz: |