Interactions of cytotoxic amino acid derivatives of tert-butylquinone with DNA and lysozyme
AuthorsVilipic, Jovana P.
Novaković, Irena T.
Zlatovic, Mario V.
Vujčić, Miroslava T.
Tufegdzic, Srdan J.
Sladić, Dušan M.
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The interactions of nine amino acid derivatives of tert-butylquinone with biomacromolecules were studied. Sodium dodecyl sulphate (SDS) gel electrophoresis and mass spectrometry confirmed the absence of modifications of lysozyme by any of the synthesized compounds. Spectrophotometric studies demonstrated hyperchromism, i.e., the existence of interactions between the quinones and calf thymus DNA (CT-DNA). Determination of the binding constants by absorption titration indicated weak interactions between the quinone derivatives and CT-DNA. The quenching of fluorescence of the intercalator ethidium bromide (EB) from the EB-CT-DNA system and of the minor groove binder Hoechst 33258 (H) from the H-CT-DNA system by the synthesized derivatives indicated interactions of the compounds and CT-DNA. Circular dichroism (CD) spectra demonstrated a non-intercalative binding mode of the quinone derivatives to CT-DNA. Molecular docking results confirmed binding to the minor groove. The electrophoretic p...attern showed no cleavage of the pUC19 plasmid in the presence of any of the synthesized compounds. The ability of the derivatives to scavenge radicals was confirmed by the 2,2-diphenyl-1-picrylhydrazyl (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.
Keywords:quinone / DNA binding / minor groove / fluorescence
Source:Journal of the Serbian Chemical Society, 2016, 81, 12, 1345-1358
- Reinforcement of the Faculty of Chemistry, University of Belgrade, towards becoming a Center of Excellence in the region of WB for Molecular Biotechnology and Food research (EU-256716)
- Interactions of natural products, their derivatives and coordination compounds with proteins and nucleic acids (RS-172055)