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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Inhibition of cyclin-dependent kinase CDK1 by oxindolimine ligands and corresponding copper and zinc complexes

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Miguel, Rodrigo Bernardi [1] ; Divina Petersen, Philippe Alexandre [2] ; Gonzales-Zubiate, Fernando A. [3] ; Oliveira, Carla Columbano [3] ; Kumar, Naresh [1] ; do Nascimento, Rafael Rodrigues [2] ; Petrilli, Helena Maria [2] ; da Costa Ferreira, Ana Maria [1]
Total Authors: 8
[1] Univ Sao Paulo, Inst Quim, Dept Quim Fundamental, BR-05508000 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Inst Fis, Dept Fis Mat & Mecan, BR-05508090 Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508000 Sao Paulo, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY; v. 20, n. 7, p. 1205-1217, OCT 2015.
Web of Science Citations: 9

Oxindolimine-copper(II) and zinc(II) complexes that previously have shown to induce apoptosis, with DNA and mitochondria as main targets, exhibit here significant inhibition of kinase CDK1/cyclin B protein. Copper species are more active than the corresponding zinc, and the free ligand shows to be less active, indicating a major influence of coordination in the process, and a further modulation by the coordinated ligand. Molecular docking and classical molecular dynamics provide a better understanding of the effectiveness and kinase inhibition mechanism by these compounds, showing that the metal complex provides a stronger interaction than the free ligand with the ATP-binding site. The metal ion introduces charge in the oxindole species, giving it a more rigid conformation that then becomes more effective in its interactions with the protein active site. Analogous experiments resulted in no significant effect regarding phosphatase inhibition. These results can explain the cytotoxicity of these metal complexes towards different tumor cells, in addition to its capability of binding to DNA, and decreasing membrane potential of mitochondria. (AU)

FAPESP's process: 10/51842-3 - Structural study of protein components of the exosome and some of its regulatory factors from Archaea and yeast
Grantee:Carla Columbano de Oliveira
Support type: Research Projects - Thematic Grants
FAPESP's process: 11/50318-1 - Development of compounds with pharmacological or medicinal interest and of systems for their transport, detection and recognition in biological media
Grantee:Ana Maria da Costa Ferreira
Support type: Research Projects - Thematic Grants
FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC