Interaction of dicentrinone, an antitrypanosomal aporphine alkaloid isolated from Ocotea puberula (Lauraceae), in cell membrane models at the air-water interface

Barbosa, Henrique; Silva, Rafael Leonardo C.G. da; Costa-Silva, Thaís A.; Tempone, André G.; Antar, Guilherme Medeiros; Lago, João Henrique G.; Caseli, Luciano

doi:10.1016/j.bioorg.2020.103978

Cited by 20 publications

(7 citation statements)

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“…The parasite viability was determined using the resazurin (Alamar Blue ® ) colorimetric method. Benznidazole was used as the standard drug, and the untreated cells were used as the negative control ( Barbosa et al, 2020 ). The mortality of the parasites induced by fractions (bioguided fractionation) was performed using the incubation of trypomastigotes at a fixed concentration of 300 µg/ml for 24 h at 37°C in a 5% CO 2 incubator.…”

Section: Methodsmentioning

confidence: 99%

(-)-T-Cadinol—a Sesquiterpene Isolated From Casearia sylvestris (Salicaceae)—Displayed In Vitro Activity and Causes Hyperpolarization of the Membrane Potential of Trypanosoma cruzi

et al. 2021

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Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and affects 6–8 million people worldwide, mainly from developing countries. The treatment is limited to two approved nitro-derivatives, nifurtimox and benznidazole, with several side effects and reduced efficacy. Casearia sylvestris has been used in folk medicine as an antiseptic and cicatrizing in skin diseases. In the present work, the hexane phase from the MeOH extract from the leaves of Casearia sylvestris afforded a fraction composed by the sesquiterpene T-cadinol, which was chemically characterized by NMR and HRMS. The activity of T-cadinol was evaluated against T. cruzi, and IC50 values of 18 (trypomastigotes) and 15 (amastigotes) µM were established. The relation between the mammalian toxicity and the antiparasitic activity resulted in a selectivity index >12. Based on this promising activity, the mechanism of action was investigated by different approaches using fluorescent-based techniques such as plasma membrane permeability, plasma membrane electric potential, mitochondrial membrane electric potential, reactive oxygen species, and the intracellular calcium (Ca2+) levels. The obtained results demonstrated that T-cadinol affected neither the parasite plasma membrane nor the electric potential of the membrane. Nevertheless, this compound induced a mitochondrial impairment, resulting in a hyperpolarization of the membrane potential, with decreased levels of reactive oxygen species. No alterations in Ca2+ levels were observed, suggesting that T-cadinol may affect the single mitochondria of the parasite. This is the first report about the occurrence of T-cadinol in C. sylvestris, and our data suggest this sesquiterpene as an interesting hit compound for future optimizations in drug discovery studies for Chagas disease.

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Section: Methodsmentioning

confidence: 99%

(-)-T-Cadinol—a Sesquiterpene Isolated From Casearia sylvestris (Salicaceae)—Displayed In Vitro Activity and Causes Hyperpolarization of the Membrane Potential of Trypanosoma cruzi

et al. 2021

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“…O alcaloide dicentrinona (45) possui atividade antiparasitária contra formas tripomastigotas de Trypanosoma cruzi (BARBOSA et al, 2020). Boldina (15) apresenta atividade larvicida (CONCEIÇÃO et al, 2020).…”

Section: Resultsunclassified

Eletroquímica – Uma Revisão De Conceitos Básicos

Cottet¹,

Appelt²,

Marcondes³

2022

Pesquisas Científicas E O Ensino De Química 3

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Direitos para esta edição cedidos à Atena Editora pelos autores. Open access publication by Atena Editora Todo o conteúdo deste livro está licenciado sob uma Licença de Atribuição Creative Commons. Atribuição-Não-Comercial-NãoDerivativos 4.0 Internacional (CC BY-NC-ND 4.0). O conteúdo dos artigos e seus dados em sua forma, correção e confiabilidade são de responsabilidade exclusiva dos autores, inclusive não representam necessariamente a posição oficial da Atena Editora. Permitido o download da obra e o compartilhamento desde que sejam atribuídos créditos aos autores, mas sem a possibilidade de alterá-la de nenhuma forma ou utilizá-la para fins comerciais.Todos os manuscritos foram previamente submetidos à avaliação cega pelos pares, membros do Conselho Editorial desta Editora, tendo sido aprovados para a publicação com base em critérios de neutralidade e imparcialidade acadêmica.A Atena Editora é comprometida em garantir a integridade editorial em todas as etapas do processo de publicação, evitando plágio, dados ou resultados fraudulentos e impedindo que interesses financeiros comprometam os padrões éticos da publicação. Situações suspeitas de má conduta científica serão investigadas sob o mais alto padrão de rigor acadêmico e ético.

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“…In continuation of our studies concerning the discovery of new antiprotozoal compounds from Lauraceae species, [18,22,23] the phytochemical analysis from P. fulva leaves yielded three known γ‐lactones: majoranolide B ( 1 ), majorenolide ( 2 ) and majorynolide ( 3 ). Other two known compounds were isolated from the roots of P. americana : lincomolide D ( 4 ) and isolinderanolide E ( 5 ), as well as one new γ‐lactone named perseanolide (3 E ,4 R )‐3‐docosylidene‐4‐hydroxy‐5‐methylideneoxolan‐2‐one; ( 6 ).…”

Section: Introductionmentioning

confidence: 90%

γ‐Lactones from Persea americana and Persea fulva – in Vitro and in Silico Evaluation of Trypanosoma cruzi Activity

Reis

Umehara

Conceição

et al. 2021

Chemistry & Biodiversity

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In the present study, five known γ‐lactones (majoranolide B – 1, majorenolide – 2, majorynolide – 3, lincomolide D – 4, and isolinderanolide E – 5), as well as a new one (perseanolide – 6), were isolated from Persea fulva and P. americana. All isolated compounds exhibited potential activity against trypomastigote forms of Trypanosoma cruzi, whereas compounds 2 (EC50 of 4.8 μM) and 6 (EC50 of 3.6 μM) displayed superior activity than the positive control benznidazole (EC50 of 16.4 μM), with selectivity index (SI) values of 17.8 and >55.6, respectively (benznidazole, SI>12.2). Molecular docking studies were performed for 1–6 against six T. cruzi molecular targets. Using this approach, we observed that, even though perseanolide (6) showed favorable docking to several studied targets, the results were especially promising for hypoxanthine phosphoribosyl transferase (PDB 1TC1). As PDB 1TC1 is associated to the transference of a monophosphorylated ribose from phosphoribosylpyrophosphate (PRPP) in the ribonucleotide synthesis pathway, this interaction may affect the survival of T. cruzi in mammalian cells. The data herein also indicate that possible intermolecular interactions between 6 and PDB 1TC1 derive from (i) hydrogen bonds in the α,β‐unsaturated‐γ‐lactone unity and (ii) hydrophobic interactions in the long‐chain alkyl group. Based on our results, perseanolide (6), reported for the first time in this work, can auspiciously contribute to future works regarding new trypanocidal agents.

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Interaction of dicentrinone, an antitrypanosomal aporphine alkaloid isolated from Ocotea puberula (Lauraceae), in cell membrane models at the air-water interface

Cited by 20 publications

References 31 publications

(-)-T-Cadinol—a Sesquiterpene Isolated From Casearia sylvestris (Salicaceae)—Displayed In Vitro Activity and Causes Hyperpolarization of the Membrane Potential of Trypanosoma cruzi

(-)-T-Cadinol—a Sesquiterpene Isolated From Casearia sylvestris (Salicaceae)—Displayed In Vitro Activity and Causes Hyperpolarization of the Membrane Potential of Trypanosoma cruzi

Eletroquímica – Uma Revisão De Conceitos Básicos

γ‐Lactones from Persea americana and Persea fulva – in Vitro and in Silico Evaluation of Trypanosoma cruzi Activity

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