https://orcid.org/0000-0001-9389-4805
Abstract
Aims: The development of safe and effective therapies for treating paracoccidioidomycosis using computational strategies were employed to discover anti-Paracoccidioides compounds. Materials & methods: We 1) collected, curated and integrated the largest library of compounds tested against Paracoccidioides spp.; 2) employed a similarity search to virtually screen the ChemBridge database and select nine compounds for experimental evaluation; 3) performed an experimental evaluation to determine the minimum inhibitory concentration and minimum fungicidal concentration as well as cytotoxicity; and 4) employed computational tools to identify potential targets for the most active compounds. Seven compounds presented activity against Paracoccidioides spp. Conclusion: These compounds are new hits with a predicted mechanisms of action, making them potentially attractive to develop new compounds.
Graphical Abstract
Supplementary data
To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2016-0184
Author contributions
VM Alves and M Pereira conceived the study. A Alves de Oliveira, VM Alves, BJ Neves and VA Fiaia Costa executed the computational analysis. A Alves de Oliveira, VM Alves, BJ Neves, EN Muratov and C Horta Andrade contributed to the computational part. L do Carmo Silva executed all the biological experiments. L do Carmo Silva, CM de Almeida Soares and M Pereira contributed to the experimental part. The manuscript was written through the contributions of all authors. All authors have approved the final version of the manuscript.
Acknowledgments
The authors gratefully thank Jon-Michael Beasley for his kind help with editing the manuscript.
Financial & competing interests disclosure
This work was supported by Ministério da Ciência e Tecnologia/Conselho Nacional de Desenvolvimento Científico e Tecnológico (MCTI/CNPq), Fundo Nacional de Desenvolvimento Científico e Tecnológico (FNDCT), Fundação de Amparo à Pesquisa do Estado de Goiás (FAPEG), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-Finance Code 001, Financiadora de Estudos e Projetos (FINEP), Programa de Apoio a Núcleos de Excelência (PRONEX), and Instituto Nacional de Ciência e Tecnologia de Estratégias de Interação Patógeno-Hospedeiro (INCT-IPH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors are also grateful to OpenEye Scientific Software, Inc. for providing academic licenses of their software. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.