Computer-aided identification of novel anti-paracoccidioidomycosis compounds.

Authors:
Bruno J Neves
Bruno J Neves
Praça Universitária com 1a Av
Brazil
Marcelo N Gomes
Marcelo N Gomes
LabMol - Laboratory for Molecular Modeling and Drug Design
Carolina H Andrade
Carolina H Andrade
Federal University of Goiás
Brazil
Maristela Pereira
Maristela Pereira
Laboratório de Biologia Molecular
Brazil

Future Microbiol 2018 10 12;13:1523-1535. Epub 2018 Oct 12.

Laboratory of Molecular Biology, Universidade Federal de Goiás, Goiânia, Goiás, 74690-900, Brazil.

Aim: The shape-based virtual screening was used for the identification of new compounds anti-paracoccidioidomycosis (PCM).

Materials & Methods: The study was performed according to the following steps: collection and curation of a dataset of quinolinyl N-oxide chalcones with anti-PCM activity, development and validation of shape-based models, application of the best model for virtual screening, and experimental validation.

Results & Conclusion: Among 31 computational hits, eight compounds showed potent antifungal activity and low cytotoxicity for mammalian cells. The checkerboard assay showed that most promising hit (compound 3) displayed additive effects with the antifungal cotrimoxazole and amphotericin B. Therefore, the shape-based virtual screening allowed us to discover promising compounds in prospective hit-to-lead optimization studies for tackling PCM.

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Source
https://www.futuremedicine.com/doi/10.2217/fmb-2018-0175
Publisher Site
http://dx.doi.org/10.2217/fmb-2018-0175DOI Listing
October 2018
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