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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.)

gamma-Lactones from Persea americana and Persea fulva - in Vitro and in Silico Evaluation of Trypanosoma cruzi Activity

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Author(s):
Reis, Isabella Mary A. [1] ; Umehara, Eric [2] ; Conceicao, Rodrigo S. [1] ; de M. Oliveira, Larissa [1] ; dos S. Junior, Manoelito Coelho [1] ; Costa-Silva, Thais A. [2] ; Amaral, Maiara [3] ; Tempone, Andre G. [3] ; Branco, Alexsandro [1] ; Lago, Joao Henrique G. [2]
Total Authors: 10
Affiliation:
[1] Univ Estadual Feira de Santana, Dept Saude, BR-44036900 Feira De Santana, BA - Brazil
[2] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210580 Santo Andre, SP - Brazil
[3] Adolfo Lutz Inst, Ctr Parasitol & Micol, BR-01246902 Sao Paulo, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: CHEMISTRY & BIODIVERSITY; v. 18, n. 9 JUL 2021.
Web of Science Citations: 0
Abstract

In the present study, five known gamma-lactones (majoranolide B - 1, majorenolide - 2, majorynolide - 3, lincomolide D - 4, and isolinderanolide E - 5), as well as a new one (perseanolide - 6), were isolated from Persea fulva and P. americana. All isolated compounds exhibited potential activity against trypomastigote forms of Trypanosoma cruzi, whereas compounds 2 (EC50 of 4.8 mu M) and 6 (EC50 of 3.6 mu M) displayed superior activity than the positive control benznidazole (EC50 of 16.4 mu M), with selectivity index (SI) values of 17.8 and >55.6, respectively (benznidazole, SI>12.2). Molecular docking studies were performed for 1-6 against six T. cruzi molecular targets. Using this approach, we observed that, even though perseanolide (6) showed favorable docking to several studied targets, the results were especially promising for hypoxanthine phosphoribosyl transferase (PDB 1TC1). As PDB 1TC1 is associated to the transference of a monophosphorylated ribose from phosphoribosylpyrophosphate (PRPP) in the ribonucleotide synthesis pathway, this interaction may affect the survival of T. cruzi in mammalian cells. The data herein also indicate that possible intermolecular interactions between 6 and PDB 1TC1 derive from (i) hydrogen bonds in the alpha,beta-unsaturated-gamma-lactone unity and (ii) hydrophobic interactions in the long-chain alkyl group. Based on our results, perseanolide (6), reported for the first time in this work, can auspiciously contribute to future works regarding new trypanocidal agents. (AU)

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
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 Opportunities: BIOTA-FAPESP Program - Regular Research Grants