Author | Silva, João Victor Silva | |
Author | Moreira, Rosiane Fernandes | |
Author | Watanabe, Luciano Almeida | |
Author | Souza, Celeste da Silva Freitas de | |
Author | Hardoim, Daiana de Jesus | |
Author | Taniwaki, Noemi Nosomi | |
Author | Bertho, Alvaro Luiz | |
Author | Teixeira, Kerolain Faoro | |
Author | Cenci, Arthur Ribeiro | |
Author | Doring, Thiago Henrique | |
Author | Cruz Júnior, José Wilmo da | |
Author | Oliveira, Aldo Sena de | |
Author | Marinho, Patrícia Santana Barbosa | |
Author | Calabrese, Kátia da Silva | |
Author | Marinho, Andrey Moacir do Rosario | |
Author | Souza, Fernando Almeida | |
Access date | 2023-01-13T14:01:33Z | |
Available date | 2023-01-13T14:01:33Z | |
Document date | 2022 | |
Citation | SILVA, João Victor Silva et al. Monomethylsulochrin isolated from biomass extract of Aspergillus sp. against Leishmania amazonensis: In vitro biological evaluation and molecular docking. Frontiers in Cellular and Infection Microbiology, v. 12, 974910, p. 1 - 17, Aug. 2022. | en_US |
ISSN | 2235-2988 | en_US |
URI | https://www.arca.fiocruz.br/handle/icict/56455 | |
Language | eng | en_US |
Publisher | Frontiers Media | en_US |
Rights | open access | |
Subject in Portuguese | Leishmania amazonensis | en_US |
Subject in Portuguese | Monometilsulochrina | en_US |
Subject in Portuguese | Microscópio eletrônico | en_US |
Subject in Portuguese | Citometria de fluxo | en_US |
Subject in Portuguese | Potencial de membrana mitocondrial | en_US |
Subject in Portuguese | CYP51 | en_US |
Subject in Portuguese | ADMET | en_US |
Title | Monomethylsulochrin isolated from biomass extract of Aspergillus sp. against Leishmania amazonensis: In vitro biological evaluation and molecular docking | en_US |
Type | Article | |
DOI | 10.3389/fcimb.2022.974910 | |
Abstract | Leishmaniasis represents a serious world health problem, with 1 billion people
being exposed to infection and a broad spectrum of clinical manifestations with a
potentially fatal outcome. Based on the limitations observed in the treatment of
leishmaniasis, such as high cost, significant adverse effects, and the potential for
drug resistance, the aim of the present study was to evaluate the leishmanicidal
activity of the compounds pseurotin A and monomethylsulochrin isolated from
the biomass extract of Aspergillus sp. The chromatographic profiles of the extract
were determined by high-performance liquid chromatography coupled with a
diode-array UV-Vis detector (HPLC-DAD-UV), and the molecular identification of
the pseurotin A and monomethylsulochrin were carried out by electrospray
ionization mass spectrometry in tandem (LC-ESI-MS-MS) and nuclear magnetic
resonance (NMR). Antileishmanial activity was assayed against promastigote and
intracellular amastigote of Leishmania amazonensis. As a control, cytotoxicity
assays were performed in non-infected BALB/c peritoneal macrophages.
Ultrastructural alterations in parasites were evaluated by transmission electron microscopy. Changes in mitochondrial membrane potential were determined by
flow cytometry. Only monomethylsulochrin inhibited the promastigote growth
(IC50 18.04 ± 1.11 μM), with cytotoxicity to peritoneal macrophages (CC50 5.09
91.63 ± 1.28 μM). Activity against intracellular amastigote forms (IC50 5.09 ± 1.06
μM) revealed an increase in antileishmanial activity when compared with
promastigotes. In addition to a statistically significant reduction in the evaluated
infection parameters, monomethylsulochrin altered the ultrastructure of the
promastigote forms with atypical vacuoles, electron-dense corpuscles in the
cytoplasm, changes at the mitochondria outer membrane and abnormal
disposition around the kinetoplast. It was showed that monomethylsulochrin
leads to a decrease in the mitochondrial membrane potential (25.9%, p =
0.0286). Molecular modeling studies revealed that monomethylsulochrin can act
as inhibitor of sterol 14-alpha-demethylase (CYP51), a therapeutic target for
human trypanosomiasis and leishmaniasis. Assessed for its drug likeness,
monomethylsulochrin follows the Lipinski Rule of five and Ghose, Veber, Egan,
and Muegge criteria. Furthermore, monomethylsulochrin can be used as a
reference in the development of novel and therapeutically useful
antileishmanial agents. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil / Universidade de São Paulo. Instituto de Física de São Carlos. Laboratório de Química Medicinal e Computacional. São Carlos, SP, Brasil. | en_US |
Affilliation | Universidade Federal do Pará. Programa de Pós-Graduação em Química. Belém, PA, Brasil. | en_US |
Affilliation | Universidade Federal do Pará. Programa de Pós-Graduação em Química. Belém, PA, Brasil. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | Instituto Adolpho Lutz. Centro de Microscopia Eletrônica. São Paulo, SP, Brasil. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instalação Central de Citometria de Fluxo. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | Universidade Federal de Santa Catarina. Departamento de Ciências Exatas e Educação. Blumenau, SC, Brasil. | en_US |
Affilliation | Universidade Federal de Santa Catarina. Departamento de Ciências Exatas e Educação. Blumenau, SC, Brasil. | en_US |
Affilliation | Universidade Federal de Santa Catarina. Departamento de Ciências Exatas e Educação. Blumenau, SC, Brasil. | en_US |
Affilliation | Universidade Federal de Santa Catarina. Departamento de Ciências Exatas e Educação. Blumenau, SC, Brasil. | en_US |
Affilliation | Universidade Federal de Santa Catarina. Departamento de Ciências Exatas e Educação. Blumenau, SC, Brasil. | en_US |
Affilliation | Universidade Federal do Pará. Programa de Pós-Graduação em Química. Belém, PA, Brasil. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | Universidade Federal do Pará. Programa de Pós-Graduação em Química. Belém, PA, Brasil. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Maranhão. Programa de Pós-Graduação em Ciências de Animais. São Luis, MA, Brasil. | en_US |
Subject | Monomethylsulochrin | en_US |
Subject | Leishmania amazonensis | en_US |
Subject | Electron microscopy | en_US |
Subject | Flow cytometry | en_US |
Subject | Mitochondrial membrane potential | en_US |
Subject | CYP51 | en_US |
Subject | ADMET | en_US |