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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Kaempferol-3-O-alpha-(3,4-di-E-p-coumaroyl)-rhamnopyranoside from Nectandra oppositifolia releases Ca2+from intracellular pools of Trypanosoma cruzi affecting the bioenergetics system

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Author(s):
Conserva, Geanne A. [1] ; Costa-Silva, Thais A. [1] ; Quiros-Guerrero, Luis M. [2, 3] ; Marcourt, Laurence [2, 3] ; Wolfender, Jean-Luc [2, 3] ; Queiroz, Emerson F. [2, 3] ; Tempone, Andre G. [4] ; Lago, Joao Henrique G. [1]
Total Authors: 8
Affiliation:
[1] Fed Univ ABC, Ctr Nat Sci & Humanities, BR-09210180 Santo Andre, SP - Brazil
[2] Univ Geneva, Sch Pharmaceut Sci, Geneva - Switzerland
[3] Univ Geneva, Inst Pharmaceut Sci Western Switzerland ISPSW, Geneva - Switzerland
[4] Adolfo Lutz Inst, Ctr Parasitol & Mycol, BR-01246000 Sao Paulo, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Chemico-Biological Interactions; v. 349, NOV 1 2021.
Web of Science Citations: 0
Abstract

Phytochemical analysis of EtOH extract from leaves of Nectandra oppositifolia afforded three flavonoids: kaempferol (1), kaempferol-3-O-alpha-rhamnopyranoside (2) and kaempferol-3-O-alpha-(3,4-di-E-p-coumaroyl)-rhamnopyranoside (3), which were characterized by NMR and ESI-HRMS. When tested against the protozoan parasite Trypanosoma cruzi, the etiologic agent of Chagas disease, flavonoids 1 and 3 were effective to kill the trypomastigotes with IC50 values of 32.0 and 6.7 mu M, respectively, while flavonoid 2 was inactive. Isolated flavonoids 1-3 were also tested in mammalian fibroblasts and showed CC50 values of 24.8, 48.7 and 153.1 mu M, respectively. Chemically, these results suggested that the free aglycone plays an important role in the bioactivity while the presence of p-coumaroyl unities linked in the rhamnoside unity is important to enhance the antitrypanosomal activity and reduce the mammalian cytotoxicity. The mechanism of cellular death was investigated for the most potent flavonoid 3 in the trypomastigotes using fluorescent and luminescent-based assays. It indicated that this compound induced neither permeabilization of the plasma membrane nor depolarization of the membrane electric potential. However, early time incubation (20 min) with flavonoid 3 resulted in a constant elevation of the Ca2+ levels inside the parasite. This effect was followed by a mitochondrial imbalance, leading to a hyperpolarization and depolarization of the mitochondrial membrane potential, with reduction of the ATP levels. During this time, the levels of reactive oxygen species levels (ROS) were unaltered. The leakage of Ca2+ from the intracellular pools can affect the bioenergetics system of T. cruzi, leading to the parasite death. Therefore, flavonoid 3 can be a useful tool for future studies against T. cruzi parasites. (AU)

FAPESP's process: 16/20633-6 - BIOACTIVE METABOLITES FROM Nectandra oppositifolia Ness. & Mart. (LAURACEAE) - MOLECULAR CHARACTERIZATION, in vitro AND in vivo ANTIPARASITIC POTENTIAL EVALUATION AND DETERMINATION OF MECHANISM OF ACTION
Grantee:Geanne Alexsandra Alves Conserva
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 21/04464-8 - Microbial and plant prototypes as drug candidates for protozoan neglected diseases and multidrug-resistant bacteria
Grantee:André Gustavo Tempone Cardoso
Support type: Regular Research Grants
FAPESP's process: 21/02789-7 - Search for bioactive metabolites with antiparasitic action in plant species from Atlantic Forest and Cerrado regions - a chemical, phenotypical, and metabolomic approach
Grantee:João Henrique Ghilardi Lago
Support type: BIOTA-FAPESP Program - Regular Research Grants
FAPESP's process: 18/18975-1 - DEREPLICATION PROFILE OF Nectandra oppositifolia Nees & Mart (LAURACEAE) - IDENTIFICATION AND MOLECULAR CARACTERIZATION OF ANTIPARASITIC METABOLITES
Grantee:Geanne Alexsandra Alves Conserva
Support type: Scholarships abroad - Research Internship - Doctorate