Telomeres and telomerase are key players in tumorogenesis. Among the various strategies proposed for telomerase inhibition or telomere uncapping, the stabilization of telomeric G-quadruplex (G4) structures is a very promising one. Additionally, G4 stabilizing ligands also act over tumors mediated by the alternative elongation of telomeres. Accordingly, the discovery of novel compounds able to act on telomeres and/or inhibit the telomerase enzyme by stabilizing DNA telomeric G4 structures as well as the development of approaches efficiently prioritizing such compounds constitute active areas of research in computational medicinal chemistry and anticancer drug discovery. In this direction, we applied a virtual screening strategy based on the rigorous application of QSAR best practices and its harmonized integration with structure-based methods. More than 600,000 compounds from commercial databases were screened, the first 99 compounds were prioritized, and 21 commercially available and structurally diverse ...
['Daimel Castillo-González', 'Jean-Louis Mergny', 'Aurore De Rache', 'Gisselle Pérez-Machado', 'Miguel Ángel Cabrera-Pérez', 'Orazio Nicolotti', 'Antonellina Introcaso', 'Giuseppe Felice Mangiatordi', 'Aurore Guédin', 'Anne Bourdoncle', 'T. M. Garrigues', 'Federico Pallardó', 'M. Natália D. S. Cordeiro', 'César Paz-y-Miño', 'Eduardo Tejera', 'Fernanda Borges', 'Maykel Cruz-Monteagudo']
Harmonization of QSAR Best Practices and Molecular Docking Provides an Efficient Virtual Screening Tool for Discovering New G-Quadruplex Ligands.