QSAR-based virtual screening of natural products database for identification of potent antimalarial hits

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dc.creatorFerreira, Letícia Tiburcio
dc.creatorBorba, Joyce Villa Verde Bastos
dc.creatorMoreira Filho, José Teófilo
dc.creatorRibeiro, Aline Rimoldi
dc.creatorAndrade, Carolina Horta
dc.creatorCosta, Fabio Trindade Maranhão
dc.date.accessioned2024-11-19T13:37:06Z
dc.date.available2024-11-19T13:37:06Z
dc.date.issued2021
dc.description.abstractWith about 400,000 annual deaths worldwide, malaria remains a public health burden in tropical and subtropical areas, especially in low-income countries. Selection of drug-resistant Plasmodium strains has driven the need to explore novel antimalarial compounds with diverse modes of action. In this context, biodiversity has been widely exploited as a resourceful channel of biologically active compounds, as exemplified by antimalarial drugs such as quinine and artemisinin, derived from natural products. Thus, combining a natural product library and quantitative structure–activity relationship (QSAR)-based virtual screening, we have prioritized genuine and derivative natural compounds with potential antimalarial activity prior to in vitro testing. Experimental validation against cultured chloroquine-sensitive and multi-drug-resistant P. falciparum strains confirmed the potent and selective activity of two sesquiterpene lactones (LDT-597 and LDT-598) identified in silico. Quantitative structure–property relationship (QSPR) models predicted absorption, distribution, metabolism, and excretion (ADME) and physiologically based pharmacokinetic (PBPK) parameters for the most promising compound, showing that it presents good physiologically based pharmacokinetic properties both in rats and humans. Altogether, the in vitro parasite growth inhibition results obtained from in silico screened compounds encourage the use of virtual screening campaigns for identification of promising natural compound-based antimalarial molecules.
dc.identifier.citationFERREIRA, Letícia Tiburcio et al. QSAR-based virtual screening of natural products database for identification of potent antimalarial hits. Biomolecules, Basel, v. 11, n. 3, e459, 2021. DOI: 10.3390/biom11030459. Disponível em: https://www.mdpi.com/2218-273X/11/3/459. Acesso em: 21 out. 2024.
dc.identifier.doi10.3390/biom11030459
dc.identifier.issne- 2218-273X
dc.identifier.urihttp://repositorio.bc.ufg.br//handle/ri/25922
dc.language.isoeng
dc.publisher.countrySuica
dc.publisher.departmentFaculdade de Farmácia - FF (RMG)
dc.rightsAcesso Aberto
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectPlasmodium falciparum
dc.subjectNatural products
dc.subjectVirtual screening
dc.subjectExperimental validation
dc.subjectQSAR
dc.subjectADME
dc.titleQSAR-based virtual screening of natural products database for identification of potent antimalarial hits
dc.typeArtigo

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