DNA cleavage mechanism by metal complexes of Cu(II), Zn(II) and VO(IV) with a schiff-base ligand.

Autor: Rodríguez MR; CEQUINOR (Centro de Química Inorgánica 'Prof. Dr. Pedro J. Aymonino'), Consejo Nacional de Investigaciones Científicas y Técnicas -CCT-La Plata, Universidad Nacional de La Plata, Bvd. 120 N 1469, La Plata, Argentina., Lavecchia MJ; CEQUINOR (Centro de Química Inorgánica 'Prof. Dr. Pedro J. Aymonino'), Consejo Nacional de Investigaciones Científicas y Técnicas -CCT-La Plata, Universidad Nacional de La Plata, Bvd. 120 N 1469, La Plata, Argentina., Parajón-Costa BS; CEQUINOR (Centro de Química Inorgánica 'Prof. Dr. Pedro J. Aymonino'), Consejo Nacional de Investigaciones Científicas y Técnicas -CCT-La Plata, Universidad Nacional de La Plata, Bvd. 120 N 1469, La Plata, Argentina., González-Baró AC; CEQUINOR (Centro de Química Inorgánica 'Prof. Dr. Pedro J. Aymonino'), Consejo Nacional de Investigaciones Científicas y Técnicas -CCT-La Plata, Universidad Nacional de La Plata, Bvd. 120 N 1469, La Plata, Argentina., González-Baró MR; INIBIOLP (Instituto de Investigaciones Bioquímicas de La Plata Rodolfo R. Brenner), Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Médicas, Universidad Nacional de La Plata 60 y 120 S/N, La Plata, Buenos Aires, Argentina., Cattáneo ER; INIBIOLP (Instituto de Investigaciones Bioquímicas de La Plata Rodolfo R. Brenner), Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Médicas, Universidad Nacional de La Plata 60 y 120 S/N, La Plata, Buenos Aires, Argentina. Electronic address: ecattaneo@med.unlp.edu.ar.
Jazyk: angličtina
Zdroj: Biochimie [Biochimie] 2021 Jul; Vol. 186, pp. 43-50. Date of Electronic Publication: 2021 Apr 16.
DOI: 10.1016/j.biochi.2021.04.002
Abstrakt: Metal ions and metal complexes are important components of nucleic acid biochemistry, participating both in regulation of gene expression and as therapeutic agents. Three new transition metal complexes of copper(II), zinc(II) and oxidovanadium(IV) with a ligand derived from o-vanillin and thiophene were previously synthesized and their antitumor properties were studied in our laboratory. To elucidate some molecular mechanisms tending to explain the cytotoxic effects observed over tumor cells, we investigated the interaction of these complexes with DNA by gel electrophoresis, UV-Vis spectroscopy, docking studies and molecular dynamics simulations. Our spectroscopy and computational results have shown that all of them were able to bind to DNA, Cu(II) complex is located in the minor groove while Zn(II) and oxidovanadium(IV) complexes act as major groove binding molecules. Interestingly, only the Cu(II) complex caused double-strand DNA nicks, consistent with its higher cytotoxic activities previously observed in tumor cell lines. We propose that the DNA-complex interaction destabilize the molecule either disrupting the phosphodiester bonds or impairing DNA replication, giving those complexes strong antitumor potential.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2021 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)
Databáze: MEDLINE
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