Navegando por Assunto "Lapachol"

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Acesso aberto (Open Access)
Avaliação da atividade esquistossomicida do lapachol e análogos
(Universidade Federal do Pará, 2018-06-29) COSTA, Erica Vanessa Souza; ENK, Martin Johannes; http://lattes.cnpq.br/1169309283832476; DOLABELA, Maria Fâni; http://lattes.cnpq.br/0458080121943649
Mansonic chistosomiasis is a worldwide parasitic disease caused by Schistosomamansoni and its treatment performed with praziquantelhas some adverse reactions. The search for new drugs to treatment of this disease is important and medicinal plants can contribute with promising new molecules, such as lapachol. The present study evaluated the schistosomicidal activity of lapachol and analogues. Lapachol was isolated from Handroanthusserratifolius by silica gel chromatography column using dichloromethane as mobile phase. This substance was treated with sulfuric acid, followed by distilled water and dichloromethaneto obtain β-lapachone. To obtain α-lapachone, lapachol was solubilized and glacial acetic acid and concentrated hydrochloric acid were added. In order to evaluate schistosomicidal activity in vitro, an experiment was carried out on adult worms of S. mansoni, and morphology, motility and mortality in optic microscopy were evaluated. The active substance was submitted to the lipid peroxidation test, Malondialdehyde Dosage (MDA) and Total Antioxidant Capacity (TEAC). In addition, the active substance was submitted to cell viability assay (MTT), using the gastric epithelial (MNP01) and gastric adenocarcinoma (ACP02)strains. The active sample was evaluatedin vivo in infected mice, where wormsmortality, oviposition decrease and damage caused by parasites in animals were evaluated. Also, a histological study of kidney and liver of infected mouse treated with β-lapachone was performed. Lapachol (yield = 2.9%) and α-lapachone (yield = 60%) were not promise as schistosomicide, with their inhibitory concentrations being 50% higher than 500μg/mL in adult worms, whereas β-lapachone(yield = 65%) was very promising against adult worms (IC50 <31.25mg/mL). Analyzes in optical microscopy showed that β-lapachone treated worms presented tremor back, curled body, and lack of movement, these alterations may be related to lipid peroxidation in parasite membrane. This compound has a low antioxidant capacity, low cytotoxicity for the MNP01 and ACP02 strains, and the selectivity index is higher than 10. In vivo study showed that β-lapachone did not reduce the number of eggs in the faeces, so it did not inhibit ovoposition, and there were not alterations in the recoveredwormsnumber, and microscopic analysis showed they had motility and their membrane was integrated. Histological studies showed there were no renal and hepatic changes. In synthesis, β- lapachoneis promising as an in vitroschistosomicide and this activity may be related to lipid peroxidation in parasite membrane. However, in vitro study did not observe this activity, pharmacokinetic factors may be influencing results divergence.
Acesso aberto (Open Access)
Planejamento e avaliação in sílica de análogos de lapachol em enzima alvo de Leishmania (Leishmania) amazonensis
(Universidade Federal do Pará, 2017-11-09) FERREIRA, Érica Patrícia dos Reis; DOLABELA, Maria Fani; http://lattes.cnpq.br/0458080121943649; SANTOS, Lourivaldo da Silva; http://lattes.cnpq.br/3232898465948962
The study aims to design and evaluate antiamastigote activity of Leishmania amazonensis and cytotoxicity Lapachol analogues. The studies predictive pharmacokinetic characteristics were performed, toxicological, biological activity and molecular docking or molecular docking. For pharmacokinetic and toxicological characteristics used the online program PreADMET while biological activities were assessed by online program Prediction Spectra of Activity is Substances (PASS). For the molecular docking analysis, the therapeutic target was selected Triponationa reductase, and the evaluation of interaction between the molecules and target this protein was performed by the virtual Molegro program docker (MVD). The extraction and isolation of Lapachol was performed and its identification was performed by nuclear magnetic resonance spectroscopy (NMR). All analogs Lapachol and are well absorbed from the intestine with the absorption ranging from 79.745% to 99.056%, furthermore inhibit the cytochrome P450 (CYP). Almost half of the molecules tested (42.1%) had moderate distribution into the central nervous system (CNS), including Lapachol, while the remainder have high distribution. The results of the toxicity of the molecules studied suggest that 63.16% are mutagenic and carcinogenic, which includes Lapachol and 10.5% and 5.26% are carcinogenic and mutagenic, respectively, but showed 21.05% not exhibit cytotoxicity. In molecular docking the substances studied showed less energy than the standard substance, although they have good interaction with energies between 94.343 to 115.635 kJ / mol. The Lapachol was isolated and identified. According with to the analogo results show that with the best characteristics was the 3,4-dihydroxy-2- (2-hydroxy-3-methylbutil) nafthalen-1 (4H) -one.