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

Overview of attention for article published in Journal of Biological Inorganic Chemistry, September 2015
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Title
Inhibition of cyclin-dependent kinase CDK1 by oxindolimine ligands and corresponding copper and zinc complexes
Published in
Journal of Biological Inorganic Chemistry, September 2015
DOI 10.1007/s00775-015-1300-4
Pubmed ID
Authors

Rodrigo Bernardi Miguel, Philippe Alexandre Divina Petersen, Fernando A. Gonzales-Zubiate, Carla Columbano Oliveira, Naresh Kumar, Rafael Rodrigues do Nascimento, Helena Maria Petrilli, Ana Maria da Costa Ferreira

Abstract

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.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 13 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 13 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 4 31%
Student > Master 4 31%
Student > Doctoral Student 1 8%
Professor 1 8%
Researcher 1 8%
Other 2 15%
Readers by discipline Count As %
Chemistry 7 54%
Biochemistry, Genetics and Molecular Biology 2 15%
Physics and Astronomy 2 15%
Agricultural and Biological Sciences 1 8%
Unspecified 1 8%
Other 0 0%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 April 2016.
All research outputs
#10,832,616
of 12,219,322 outputs
Outputs from Journal of Biological Inorganic Chemistry
#313
of 368 outputs
Outputs of similar age
#230,923
of 276,629 outputs
Outputs of similar age from Journal of Biological Inorganic Chemistry
#4
of 5 outputs
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