Predição do comportamento farmacocinético, toxicidade e de atividades biológicas de alcaloides isolados de Geissospermum laeve (Vell.) Miers

Abstract

O presente trabalho realizou estudos in silico com o objetivo de predizer as atividades farmacocinéticas, toxicológicas e biológicas de alcaloides isolados de Geissospermum laeve. Os desenhos das moléculas e análises físico-químicas foram feitas no ChemSketch e Chemicalize.org, o comportamento farmacocinético e toxicidade foram realizadas por comparação nos programas PreADMET e PASS online. Os resultados descrevem que as moléculas demonstram bom comportamento farmacocinético e biodisponibilidade, com destaque para a Geissosquizina que apresenta alta permeabilidade gastrointestinal, depuração aceitável, sendo metabolizada pela CYP 3A4 e maior interação com receptotres-alvos. A Pereirina e Vellosiminol apresentaram atividades sobre neuroreceptores, enquanto que a Flavopererina demostrou atividades de modulação enzimática, dessa forma essas moléculas destacaram-se quanto às atividades biológicas apresentadas. Todas as substancias se apresentaram tóxicas e mutagênicas, sendo necessários estudos aprofundados que auxiliem a elucidação do índice de seletividade das mesmas. Ao considerar os aspectos farmacocinéticos, toxicológicos e biológicos destacamos que a Pereirina e o Vellosiminol apresentam resultados mais promissores.

Anonaine from Annona crassiflora inhibits glutathione S-transferase and improves cypermethrin activity on Rhipicephalus (Boophilus) microplus (Canestrini, 1887)

“…The predicted ADMET properties of anonaine with different parameters analyzed by the PreADMET tool shown in Supplementary Table 2, suggest that anonaine has moderate toxicity and no carcinogenic potential. All values obtained in the results with anonaine were compared to standard values reported in the literature (Ames et al, 1972;Yee, 1997;Van De Waterbeemd and Gifford, 2003;Alliance, 2016;Wadapurkar et al, 2018;Ferreira et al, 2020;Pereira, 2021;Tong et al, 2021). Also, it is suggested that natural alkaloid anonaine is less toxic to mammals than cypermethrin.…”

Cytotoxicity and Genotoxicity Evaluation of Zanthoxylum rhoifolium Lam and In Silico Studies of Its Alkaloids

“…For the oral toxicity study, the ProTox-II online server [ 52 ] was used, based on the 50% lethal dose (LD 50 ), following the classification of this potential into the following classes: fatal if ingested—class I (LD 50 ≤ 5mg/kg) and class II (LD 50 between 5 and 50 mg/kg); toxic if ingested—class III (LD 50 between 50 and 300 mg/kg); harmful if ingested—class IV (LD 50 between 300 and 2000 mg/kg); may be harmful if ingested—class V (LD 50 between 2000 and 5000 mg/kg); non-toxic—class VI (LD 50 ≥ 5000 mg/kg) [ 53 ].…”

Biological activity an in silico toxicity of phenolic compounds found in cupuaçu seed (Theobroma grandiflorum)

“…All structures showed low permeability in MDCK cells, with the following results: isoscutelarein A: 0.99703, theograndin I: 0.0448005, Theograndin II: 0.045115, hypolaetin A: 0.542677 and hypolaetin B: 0.0446855 (Table 2). MDCK (Madin-Darby canine kidney) cells come from the kidneys of Madin-Darby dogs which, when grown in the laboratory, form structures like ducts, differentiating into columnar epithelial cells with semipermeable membranes with junctions similar to Caco-2 cells, exhibiting features that resemble the epithelial cells found in kidney tubules (Ferreira, Brandão & Dolabela, 2020). MDCK cells are widely used to study renal distal tubular physiology through the transport of substances and ions (Sousa, Freitas & Storpirtis, 2007).…”

“…They are frequently used in substance toxicity studies, as they play a fundamental role in evaluating the harmful effects of different substances in the aquatic environment, being very sensitive to toxic agents. Furthermore, they are important in many food chains, being a significant source of food for fish, in addition to having a relatively short life cycle, a significant parameter for evaluating acute and subchronic toxicity (Ferreira et al, 2020).…”