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Open AccessArticle

Flavopereirine—An Alkaloid Derived from Geissospermum vellosii—Presents Leishmanicidal Activity In Vitro

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Post-Graduate Program in Pharmaceutical Sciences, Federal University of Pará, Belém, PA 66075-110, Brazil
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Laboratory of Immunomodulation and Protozoology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ 21040-900, Brazil
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Post-Graduate Program in Pharmaceutical Innovation, Federal University of Pará, Belém, PA 66075-110, Brazil
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College of Chemistry, Federal University of Pará, Belém, PA 66075-110, Brazil
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Faculty of Pharmacy, Federal University of Pará, Belém, PA 66075-110, Brazil
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Emílio Goeldi Paraense Museum, Coordination of Botany, Ministry of Science, Technology, Innovation and Communications, Belém, PA 66077-530, Brazil
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Evandro Chagas Institute, National Health Foundation, BR-316 Highway km 7, Ananindeua, PA 67030-000, Brazil
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US Centers for Disease Control and Prevention (CDC), Atlanta, GA 30329, USA
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Oxidative Stress Research Lab, Institute of Biological Sciences (ICB), Federal University of Pará, Belém, PA 66075-110, Brazil
*
Author to whom correspondence should be addressed.
Academic Editors: Marcello Locatelli, Simone Carradori and Andrei Mocan
Molecules 2019, 24(4), 785; https://doi.org/10.3390/molecules24040785
Received: 24 December 2018 / Revised: 25 January 2019 / Accepted: 27 January 2019 / Published: 21 February 2019
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
Chemotherapy is limited in the treatment of leishmaniasis due to the toxic effects of drugs, low efficacy of alternative treatments, and resistance of the parasite. This work assesses the in vitro activity of flavopereirine on promastigote cultures of Leishmania amazonensis. In addition, an in silico evaluation of the physicochemical characteristics of this alkaloid is performed. The extract and fractions were characterized by thin-layer chromatography and HPLC-DAD, yielding an alkaloid identified by NMR. The antileishmanial activity and cytotoxicity were assayed by cell viability test (MTT). The theoretical molecular properties were calculated on the Molinspiration website. The fractionation made it possible to isolate a beta-carboline alkaloid (flavopereirine) in the alkaloid fraction. Moreover, it led to obtaining a fraction with greater antileishmanial activity, since flavopereirine is very active. Regarding the exposure time, a greater inhibitory effect of flavopereirine was observed at 24 h and 72 h (IC50 of 0.23 and 0.15 μg/mL, respectively). The extract, fractions, and flavopereirine presented low toxicity, with high selectivity for the alkaloid. Furthermore, flavopereirine showed no violation of Lipinski’s rule of five, showing even better results than the known inhibitor of oligopeptidase B, antipain, with three violations. Flavopereirine also interacted with residue Tyr-499 of oligopeptidase B during the molecular dynamics simulations, giving a few insights of a possible favorable mechanism of interaction and a possible inhibitory pathway. Flavopereirine proved to be a promising molecule for its antileishmanial activity. View Full-Text
Keywords: leishmania; Geissospermum vellosii; apocynaceae; oligopeptidase B; flavopereirine; medicinal chemistry; in silico modeling leishmania; Geissospermum vellosii; apocynaceae; oligopeptidase B; flavopereirine; medicinal chemistry; in silico modeling
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da Silva e Silva, J.V.; Cordovil Brigido, H.P.; Oliveira de Albuquerque, K.C.; Miranda Carvalho, J.; Ferreira Reis, J.; Vinhal Faria, L.; Coelho-Ferreira, M.R.; Silveira, F.T.; da Silva Carneiro, A.; Percário, S.; do Rosário Marinho, A.M.; Dolabela, M.F. Flavopereirine—An Alkaloid Derived from Geissospermum vellosii—Presents Leishmanicidal Activity In Vitro. Molecules 2019, 24, 785.

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