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

摘要: The interaction of the Cu(II) drugs CuL(NO3) and CuL′(NO3) (HL is pyridine-2-carbaldehyde thiosemicarbazone HL′ 4N-methylthiosemicarbazone, in water named [CuL]+ [CuL′]+) with [poly(dA–dT)]2, [poly(dG–dC)]2, calf thymus (CT) DNA has been probed aqueous solution at pH 6.0, I = 0.1 M, T = 25 °C by absorbance, fluorescence, circular dichroism, viscosity measurements. results reveal that these act as groove binders a site size n = 6–7, whereas they external [poly(dG–dC)]2 and/or CT-DNA, thus establishing overall electrostatic n = 1. binding constants [CuL′]+ were slightly larger than [CuL]+. title compounds display some cleavage activity presence thiols, bringing about rupture strands reactive oxygen species formed reoxidation Cu(I) to Cu(II); this feature was not observed absence thiols. Mutagenic assays performed both S9 mix, Ames test on TA 98, 100, 102, negative. Weak genotoxic detected for [CuL′]+, significative dose–response effect which shown be more cytotoxic 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation assays. Methylation terminal NH2 group enhances antiproliferative thiosemicarbazones.