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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: CHEMISTRY & BIODIVERSITY; v. 18, n. 9 JUL 2021.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 18/07885-1 - Biomoléculas oriundas de espécies vegetais de áreas remanescentes da Mata Atlântica e do Cerrado para tratamento de doenças tropicais negligenciadas - aspectos químicos e farmacológicos
• Beneficiário: João Henrique Ghilardi Lago
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Regular
• Processo FAPESP: 21/02789-7 - Busca de metabólitos bioativos com ação antiparasitária em espécies vegetais de regiões de Mata Atlântica e Cerrado - uma abordagem química, fenotípica e metabolômica
• Beneficiário: João Henrique Ghilardi Lago
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Regular