Publication Type Journal Article
Title Structure-based virtual screening toward the discovery of novel inhibitors of the DNA repair activity of the human apurinic/apyrimidinic endonuclease 1
Authors Patricia S. Guerreiro Silvia G. Estacio F. J. N. Antunes Ana S. Fernandes Pedro F. Pinheiro Joao G. Costa Matilde Castro Joana P. Miranda Rita C. Guedes Nuno G. Oliveira
Groups BioMol
Journal CHEMICAL BIOLOGY \& DRUG DESIGN
Year 2016
Month December
Volume 88
Number 6
Pages 915-925
Abstract The DNA repair activity of human apurinic/apyrimidinic endonuclease 1 (APE1) has been recognized as a promising target for the development of small-molecule inhibitors to be used in combination with anticancer agents. In an attempt to identify novel inhibitors of APE1, we present a structure-based virtual screening (SBVS) study based on molecular docking analysis of the compounds of NCI database using the GOLD 5.1.0 (Genetic Optimization for Ligand Docking) suite of programs. Compounds selected in this screening were tested with a fluorescence-based APE1 endonuclease activity assay. Two compounds (37 and 41) were able to inhibit the multifunctional enzyme APE1 in the micromolar range, while compound 22 showed inhibitory effects at nanomolar concentrations. These results were confirmed by a plasmid DNA nicking assay. In addition, the potential APE1 inhibitors did not affect the cell viability of non-tumor MCF10A cells. Overall, compounds 22, 37, and 41 appear to be important scaffolds for the design of novel APE1 inhibitors and this study highlights the relevance of in silico-based approaches as valuable tools in drug discovery.
DOI http://dx.doi.org/10.1111/cbdd.12826
ISBN
Publisher WILEY
Book Title
ISSN 1747-0277
EISSN 1747-0285
Conference Name
Bibtex ID ISI:000387362800014
Observations
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