Flavopereirine—An alkaloid derived from geissospermum vellosii—Presents leishmanicidal activity in vitro

This research was funded by the National Council for Scientific and Technological Development [CNPq; Scholarship DT 310608/2013-9 Universal; 483894/2012-5] and PROPESP/UFPAFederal University of Pará. Post-Graduate Program in Pharmaceutical Sciences. Belém, PA, Brazil / Fundação Oswaldo Cruz. Oswaldo Cruz Institute. Laboratory of Immunomodulation and Protozoology. Rio de Janeiro, RJ, Brazil.Federal University of Pará. Post-Graduate Program in Pharmaceutical Innovation. Belém, PA, Brazil.Federal University of Pará. Post-Graduate Program in Pharmaceutical Sciences. Belém, PA, Brazil.Federal University of Pará. College of Chemistry. Belém, PA, Brazil.Federal University of Pará. Faculty of Pharmacy. Belém, PA, Brazil.Ministry of Science, Technology, Innovation and Communications. Emílio Goeldi Paraense Museum. Coordination of Botany. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Leishmanioses Prof. Dr. Ralph Lainson. Ananindeua, PA, Brasil.Federal University of Pará. Faculty of Pharmacy. Belém, PA, Brazil.US Centers for Disease Control and Prevention. Atlanta, GA, USA / Federal University of Pará. Institute of Biological Sciences. Oxidative Stress Research Lab. Belém, PA, Brazil.Federal University of Pará. College of Chemistry. Belém, PA, Brazil.Federal University of Pará. Post-Graduate Program in Pharmaceutical Sciences. Belém, PA, Brazil / Federal University of Pará. Post-Graduate Program in Pharmaceutical Innovation. Belém, PA, Brazil.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