Interactions of cytotoxic amino acid derivatives of tert-butylquinone with DNA lysozyme

Abstract

The interactions of nine amino acid derivatives of tert-butylquinone with biomacromolecules were studied. SDS electrophoresis and mass spectrometry confirmed the absence of modifications of lysozyme by any of the synthesized compounds. Spectrophotometric studies demonstrated hyperchromism, i.e. existence of interactions between the quinones and CT-DNA. Determination of binding constant by absorption titration indicates weak interactions between quinone derivatives and CT-DNA. The quenching of fluorescence of intercalator ethidium bromide from EB-CT-DNA system and of minor groove binder Hoechst 33258 from H-CT-DNA system by the synthesized derivatives indicates interactions of compounds and CT-DNA. CD spectra demonstrate non-intercalative binding mode of quinone derivaties to CT-DNA. Molecular docking results confirm binding to the minor groove. Electrophoretic pattern showed no cleavage of pUC19 plasmid in the presence of any of the synthesized compounds. The ability of the derivatives to scavenge radicals was confirmed by DPPH test. All the presented results suggest that the DNA minor groove binding is the principal mechanism of action of the examined amino acid derivatives. [Projekat Ministarstva nauke Republike Srbije, br. 172055]

Keywords

• quinone
• DNA binding
• minor groove
• fluorescence