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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.)

Antitrypanosomal Activity of Acetogenins Isolated from the Seeds of Porcelia macrocarpa Is Associated with Alterations in Both Plasma Membrane Electric Potential and Mitochondrial Membrane Potential

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Oliveira, Emerson A. [1] ; Brito, Ivanildo A. [2] ; Lima, Marta L. [3] ; Romanelli, Maiara [3] ; Moreira-Filho, Jose T. [4] ; Neves, Bruno J. [4, 5] ; Andrade, Carolina H. [4] ; Sartorelli, Patricia [1] ; Tempone, Andre G. [3] ; Costa-Silva, Thais A. [2] ; Lago, Joao Henrique G. [2]
Total Authors: 11
[1] Univ Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, BR-09972270 Sao Paulo - Brazil
[2] Fed Univ ABC, Ctr Nat & Human Sci, BR-09606045 Sao Paulo - Brazil
[3] Adolfo Lutz Inst, Ctr Parasitol & Mycol, BR-01246000 Sao Paulo - Brazil
[4] Univ Fed Goias, Fac Pharm, BR-74605170 Goiania, Go - Brazil
[5] Univ Ctr Anapolis, Lab Cheminformat, BR-75083515 Anapolis, Go - Brazil
Total Affiliations: 5
Document type: Journal article
Source: Journal of Natural Products; v. 82, n. 5, p. 1177-1182, MAY 2019.
Web of Science Citations: 0

As part of a drug discovery program aimed at the identification of anti-Trypanosoma cruzi metabolites from Brazilian flora, four acetogenins (1-4) were isolated from the seeds of Porcelia macrocarpa and were identified by NMR spectroscopy and HRESIMS. The new compounds 1 and 2 displayed activity against the trypomastigote (IC50 = 0.4 and 3.6 mu M) and amastigote (IC50 = 23.0 and 27.7 mu M) forms. The structurally related known compound 3 showed less potency to the amastigotes, with an IC50 value of 58 mu M, while the known compound 4 was inactive. To evaluate the potential mechanisms for parasite death, parameters were evaluated by fluorometric assays: (i) plasma membrane permeability, (ii) plasma membrane electric potential (Delta Psi(m)), (iii) reactive oxygen species production, and (iv) mitochondrial membrane potential (Delta Psi(m)). The results obtained indicated that compounds 1 and 2 depolarize plasma membranes, affecting Delta Psi(p), and Delta Psi(m) and contributing to the observed cellular damage and disturbing the bioenergetic system. In silico studies of pharmacokinetics and toxicity (ADMET) properties predicted that all compounds were nonmutagenic, noncarcinogenic, nongenotoxic, and weak hERG blockers. Additionally, none of the isolated acetogenins 1-4 were predicted as pan-assay interference compounds. (AU)

FAPESP's process: 18/10279-6 - Selection and Optimization of New Drug Candidates for Leishmaniasis and Chagas Disease
Grantee:André Gustavo Tempone Cardoso
Support Opportunities: Regular Research Grants
FAPESP's process: 18/07885-1 - Biomolecules from plant species of remnant areas of the Atlantic Forest and Cerrado to treat neglected tropical diseases - chemical and pharmacological aspects
Grantee:João Henrique Ghilardi Lago
Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants