title: Quantum-chemical study of interactions of trans-resveratrol with guanine-thymine dinucleotide and DNA-nucleobases.
abstract: Trans-resveratrol, a natural phytoalexin present in red wine and grapes, has gained considerable attention because of its antiproliferative, chemopreventive and proapoptotic activity against human cancer cells. The accurate quantum-chemical computations based on the density functional theory (DFT) and ab initio second-order Møller-Plesset perturbation method (MP2) have been performed for the first time to study interactions of trans-resveratrol with guanine-thymine dinucleotide and DNA-derived nitrogenous bases: adenine, guanine, cytosine and thymine in vacuum and water medium. This compound is found to show high affinity to nitrogenous bases and guanine-thymine dinucleotide. The electrostatic interactions from intermolecular hydrogen bonding increase the stability of complexes studied. In particular, significantly strong hydrogen bonds between 4'-H atom of trans-resveratrol and imidazole nitrogen as well as carbonyl oxygen atoms of nucleobases studied stabilize these systems. The stabilization energies computed reveal that the negatively charged trans-resveratrol-dinucleotide complex is more energetically stable in water medium than in vacuum. MP2 method gives more reliable and significantly high values of stabilization energy of trans-resveratrol-dinucleotide, trans-resveratrol-guanine and trans-resveratrol-thymine complexes than B3LYP exchange-correlation functional because it takes into account London dispersion energy. According to the results, in the presence of trans-resveratrol the 3'-5' phosphodiester bond in dinucleotide can be cleaved and the proton from 4'-OH group of trans-resveratrol migrates to the 3'-O atom of dinucleotide. It is concluded that trans-resveratrol is able to break the DNA strand. Hence, the findings obtained help understand antiproliferative and anticancer properties of this polyphenol.
authors.affiliation: Department of Theoretical Chemistry, Faculty of Chemistry, A. Mickiewicz University ul, Grunwaldzka 6, 60-780 Poznań, Poland. dmkwant@amu.edu.pl
authors.forename: Damian
authors.initials: D
authors.lastname: Mikulski
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Szeląg
authors.forename: Marcin
authors.initials: M
authors.lastname: Molski
mesh_terms: D000225:Adenine / Q000737:chemistry / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D003596:Cytosine / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D053960:DNA Breaks / Q000187:drug effects*; D006147:Guanine / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D009690:Nucleic Acid Conformation / Q000187:drug effects; D011789:Quantum Theory; D000077185:Resveratrol; D055672:Static Electricity; D013267:Stilbenes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013816:Thermodynamics; D013941:Thymine / Q000737:chemistry / Q000378:metabolism*; D014618:Vacuum; D014867:Water / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D014867:Water; D006147:Guanine; D003596:Cytosine; D004247:DNA; D000225:Adenine; D000077185:Resveratrol; D013941:Thymine