In silico, in vitro and in vivo evaluation of natural Bignoniaceous naphthoquinones in comparison with atovaquone targeting the selection of potential antimalarial candidates
| Autor: | Tatiane Freitas Borgati, Alaíde Braga de Oliveira, Carlos Alberto Tagliati, Larissa Camila Ribeiro de Souza, Maria Fernanda Alves do Nascimento |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Swine In silico Plasmodium falciparum Drug Evaluation Preclinical Pharmacology Toxicology Madin Darby Canine Kidney Cells Antimalarials Mice 03 medical and health sciences chemistry.chemical_compound Dogs Drug Delivery Systems 0302 clinical medicine In vivo medicine Animals Humans Computer Simulation Cytotoxicity Atovaquone Lapachol biology Chemistry In vitro toxicology Hep G2 Cells biology.organism_classification In vitro 030104 developmental biology A549 Cells 030220 oncology & carcinogenesis LLC-PK1 Cells Female Caco-2 Cells Naphthoquinones medicine.drug |
| Zdroj: | Toxicology and Applied Pharmacology. 401:115074 |
| ISSN: | 0041-008X |
| Popis: | The natural naphthoquinones lapachol, α- and β-lapachone are found in Bignoniaceous Brazilian plant species of the Tabebuia genus (synonym Handroanthus) and are recognized for diverse bioactivities, including as antimalarial. The aim of the present work was to perform in silico, in vitro and in vivo studies to evaluating the antimalarial potential of these three naphthoquinones in comparison with atovaquone, a synthetic antimalarial. The ADMET properties of these compounds were predicted in silico by the preADMET program. The in vitro toxicity assays were experimentally determined in immortalized and tumoral cells from different organs. In vivo acute oral toxicity was also evaluated for lapachol. Several favorable pharmacokinetics data were predicted although, as expected, high cytotoxicity was experimentally determined for β-lapachone. Lapachol was not cytotoxic or showed low cytotoxicity to all of the cells assayed (HepG2, A549, Neuro 2A, LLC-PK1, MRC-5), it was nontoxic in the acute oral test and disclosed the best parasite selectivity index in the in vitro assays against chloroquine resistant Plasmodium falciparum W2 strain. On the other hand, α- and β-lapachone were more potent than lapachol in the antiplasmodial assays but with low parasite selectivity due to their cytotoxicity. The diversity of data here reported disclosed lapachol as a promising candidate to antimalarial drug development. |
| Databáze: | OpenAIRE |
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