Antileishmanial activity of cordiaquinone E towards Leishmania (Leishmania) amazonensis.

Autor: Rodrigues RRL; Laboratório de Doenças Infecciosas, Campus Ministro Reis Velloso, Universidade Federal do Delta do Parnaíba, 64202-020 Parnaíba, PI, Brazil., Nunes TAL; Laboratório de Doenças Infecciosas, Campus Ministro Reis Velloso, Universidade Federal do Delta do Parnaíba, 64202-020 Parnaíba, PI, Brazil., de Araújo AR; Núcleo de Pesquisa em Biodiversidade e Biotecnologia, Campus Ministro Reis Velloso, Universidade Federal do Delta do Parnaíba, 64202-020 Parnaíba, PI, Brazil., Marinho Filho JDB; Laboratório de Cultura de Células do Delta, Campus Ministro Reis Velloso, Universidade Federal do Delta do Parnaíba, 64202-020 Parnaíba, PI, Brazil., da Silva MV; Laboratório de Imunologia e Parasitologia, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, 38025-180 Uberaba, MG, Brazil., Carvalho FAA; Núcleo de Pesquisas em Plantas Medicinais, Campus Ministro Petrônio Portella, Universidade Federal do Piauí, Teresina 64049-550, Piauí, Brazil., Pessoa ODL; Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, 60.021-970 Fortaleza, CE, Brazil., Freitas HPS; Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, 60.021-970 Fortaleza, CE, Brazil., Rodrigues KADF; Laboratório de Doenças Infecciosas, Campus Ministro Reis Velloso, Universidade Federal do Delta do Parnaíba, 64202-020 Parnaíba, PI, Brazil., Araújo AJ; Laboratório de Cultura de Células do Delta, Campus Ministro Reis Velloso, Universidade Federal do Delta do Parnaíba, 64202-020 Parnaíba, PI, Brazil. Electronic address: anajersia@ufpi.edu.br.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2021 Jan; Vol. 90, pp. 107124. Date of Electronic Publication: 2020 Nov 07.
DOI: 10.1016/j.intimp.2020.107124
Abstrakt: Leishmaniasis is caused by several protozoan species of Leishmania, and being endemically present in 98 countries around the world, it is also a severe public-health problem. The available antileishmanial drugs are toxic and yet present risks of recurrent infection. Efforts to find new, effective, and safe oral agents for the treatment of leishmaniasis are continuing throughout the world. This work aimed to evaluate the antileishmania activity of cordiaquinone E (CORe), isolated from the roots of Cordia polycephala (Lam.) I. M. Johnston. Cytotoxicity, and possible mechanisms of action against promastigote and amastigote forms of Leishmania amazonensis were examined. CORe was effective in inhibiting promastigote (IC 50 4.5 ± 0.3 µM) and axenic amastigote (IC 50 2.89 ± 0.11 µM) growth in concentrations found non-toxic for the host cell (CC 50 246.81 ± 14.5 µM). Our results revealed that CORe presents direct activity against the parasite, inducing cell death by apoptosis. CORe present greater activity against intracellular amastigotes (EC 50 1.92 ± 0.2 µM), yet with much higher selectivity indexes than the reference drugs, being respectively more benign towards RAW 264.7 macrophages than meglumine antimoniate and amphotericin B, (respectively by 4.68 and 42.84 fold). The antiamastigote activity was associated with increased TNF-α, IL-12, NO, and ROS levels, as well as decreased IL-10 levels. These results encourage the progression of studies on this compound for the development of new leishmanicidal agents.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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