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Identification of a new antifungal compound against isocitrate lyase of Paracoccidioides brasiliensis.
Future Microbiol. 2019 12; 14:1589-1606.FM

Abstract

Aim:

To perform virtual screening of compounds based on natural products targeting isocitrate lyase of Paracoccidioides brasiliensis. Materials & methods: Homology modeling and molecular dynamics simulations were applied in order to obtain conformational models for virtual screening. The selected hits were tested in vitro against enzymatic activity of ICL of the dimorphic fungus P. brasiliensis and growth of the Paracoccidioides spp. The cytotoxicity and selectivity index of the compounds were defined. Results & conclusion: Carboxamide, lactone and β-carboline moieties were identified as interesting chemical groups for the design of new antifungal compounds. The compounds inhibited ICL of the dimorphic fungus P. brasiliensis activity. The compound 4559339 presented minimum inhibitory concentration of 7.3 μg/ml in P. brasiliensis with fungicidal effect at this concentration. Thus, a new potential antifungal against P. brasiliensis is proposed.

Authors+Show Affiliations

LBM - Laboratory of Molecular Biology, Universidade Federal de Goiás, Goiânia, Goiás, 74690-900, Brazil. Collaborative Nucleus of Biosystems, Universidade Federal de Goiás, Jataí, Goiás, 75804-020, Brazil.Collaborative Nucleus of Biosystems, Universidade Federal de Goiás, Jataí, Goiás, 75804-020, Brazil. UNIFIMES, Centro Universitário de Mineiros, Mineiros, Goiás, 75833-130, Brazil.LBM - Laboratory of Molecular Biology, Universidade Federal de Goiás, Goiânia, Goiás, 74690-900, Brazil.LBM - Laboratory of Molecular Biology, Universidade Federal de Goiás, Goiânia, Goiás, 74690-900, Brazil.LBM - Laboratory of Molecular Biology, Universidade Federal de Goiás, Goiânia, Goiás, 74690-900, Brazil.Collaborative Nucleus of Biosystems, Universidade Federal de Goiás, Jataí, Goiás, 75804-020, Brazil.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31990208

Citation

da Silva, Luciane S., et al. "Identification of a New Antifungal Compound Against Isocitrate Lyase of Paracoccidioides Brasiliensis." Future Microbiology, vol. 14, 2019, pp. 1589-1606.
da Silva LS, Barbosa UR, Silva LDC, et al. Identification of a new antifungal compound against isocitrate lyase of Paracoccidioides brasiliensis. Future Microbiol. 2019;14:1589-1606.
da Silva, L. S., Barbosa, U. R., Silva, L. D. C., Soares, C. M., Pereira, M., & da Silva, R. A. (2019). Identification of a new antifungal compound against isocitrate lyase of Paracoccidioides brasiliensis. Future Microbiology, 14, 1589-1606. https://doi.org/10.2217/fmb-2019-0166
da Silva LS, et al. Identification of a New Antifungal Compound Against Isocitrate Lyase of Paracoccidioides Brasiliensis. Future Microbiol. 2019;14:1589-1606. PubMed PMID: 31990208.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of a new antifungal compound against isocitrate lyase of Paracoccidioides brasiliensis. AU - da Silva,Luciane S, AU - Barbosa,Uessiley R, AU - Silva,Lívia do C, AU - Soares,Célia Ma, AU - Pereira,Maristela, AU - da Silva,Roosevelt A, Y1 - 2020/01/28/ PY - 2020/1/29/pubmed PY - 2020/5/29/medline PY - 2020/1/29/entrez KW - Paracoccidioides brasiliensis KW - antifungal compounds KW - isocitrate lyase KW - molecular dynamics KW - natural products KW - virtual screening SP - 1589 EP - 1606 JF - Future microbiology JO - Future Microbiol VL - 14 N2 - Aim: To perform virtual screening of compounds based on natural products targeting isocitrate lyase of Paracoccidioides brasiliensis. Materials & methods: Homology modeling and molecular dynamics simulations were applied in order to obtain conformational models for virtual screening. The selected hits were tested in vitro against enzymatic activity of ICL of the dimorphic fungus P. brasiliensis and growth of the Paracoccidioides spp. The cytotoxicity and selectivity index of the compounds were defined. Results & conclusion: Carboxamide, lactone and β-carboline moieties were identified as interesting chemical groups for the design of new antifungal compounds. The compounds inhibited ICL of the dimorphic fungus P. brasiliensis activity. The compound 4559339 presented minimum inhibitory concentration of 7.3 μg/ml in P. brasiliensis with fungicidal effect at this concentration. Thus, a new potential antifungal against P. brasiliensis is proposed. SN - 1746-0921 UR - https://www.unboundmedicine.com/medline/citation/31990208/Identification_of_a_new_antifungal_compound_against_isocitrate_lyase_of_Paracoccidioides_brasiliensis_ L2 - http://www.futuremedicine.com/doi/full/10.2217/fmb-2019-0166?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -