Identification of Eschweilenol C in derivative of Terminalia fagifolia Mart. and green synthesis of bioactive and biocompatible silver nanoparticles Alyne Rodrigues de Araujo a,b , Joilson Ramos-Jesus b , Taiane Maria de Oliveira b , Andressa Maria A. de Carvalho c , Paulo Humberto M. Nunes d , Tatiane Caroline Daboit c , Ana P. Carvalho e , Maria Fátima Barroso e , Miguel Peixoto de Almeida f , Alexandra Plácido g,h , Artur Rodrigues g , Camila C. Portugal g , Renato Socodato g , João B. Relvas g , Cristina Delerue-Matos e , Durcilene Alves da Silva a,b , Peter Eaton f , José Roberto de Souza de A. Leite b,i , ⁎ a Programa de Pós-Graduação em Biotecnologia, RENORBIO, Brazil b Núcleo de Pesquisa em Biodiversidade e Biotecnologia, BIOTEC, UFPI, Parnaíba, PI, Brazil c Grupo de Estudos Avançados em Micologia Médica, GEAMICOL, UFPI, Parnaíba, PI, Brazil d Núcleo de Pesquisa em Plantas Medicinais, NPPM, UFPI, Teresina, PI, Brazil e LAQV/REQUIMTE, Instituto Superior de Engenharia, Instituto Politécnico do Porto, Portugal f LAQV/REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Portugal g Instituto de Investigação e Inovação em Saúde (i3S) e Instituto de Biologia Molecular e Celular, IBMC, Porto, Portugal h Bioprospectum, Lda, UPETC, Porto, Portugal i Nucleo de Pesquisa em Morfologia e Imunologia Aplicada, NuPMIA, Area Morfologia, Faculdade de Medicina, Universidade de Brasília (UnB), Brasília, Brazil Keywords: Ellagic acid Metallic nanoparticles Terminalia sp. Antioxidant Antimicrobial Fonsecaea pedrosoi ABSTRACT A green synthetic route was developed to prepare silver nanoparticles (AgNPs) in aqueous solution for biological applications. Eschweilenol C, a compound derivative ellagic acid was identified as the main constituent of the aqueous fraction of the ethanolic extract of Terminalia fagifolia Mart. by NMR analysis. In the green synthesis, the ethanolic extract of T. fagifolia and its aqueous fraction were used to promote silver reduction and nanoparticle stabilization. The synthesized AgNPs presented a spherical or polygonal morphology shape by TEM analysis and AgNPs showed high levels of antioxidant and considerable antibacterial and antifungal activities. Synthesized nanoparticles presented significant antioxidant activity by sequestration of DPPH and ABTS radicals, in addition to iron reduction (FRAP assay) and measurement of antioxidant capacity in ORAC units, in addition, AgNP synthesized with the aqueous fraction also demonstrated antioxidant potential in microglial cells. Gram-positive and Gram-negative bacteria were susceptible to growth inhibition by the nanoparticles, among which the AgNPs formed by the ethanolic extract was the most effective. The data obtained by AFM images suggested that AgNPs could lead to the lysis of bacteria and subsequent death. The antifungal assays showed high efficiency against yeasts and dermatophytes. This work represents the first description of antifungal activity by AgNPs against Fonsecaea pedrosoi, the etiologic agent of chromoblastomycosis. In relation to biocompatibility, the AgNPs in- duced lower haemolysis than AgNO 3 . 1. Introduction Despite efforts to discover new drugs for the treatment of infectious diseases, pathogens have shown versatility in the development of sev- eral antimicrobial resistance mechanisms. Infectious diseases remain a recognized worldwide health problem and, in this context, Abbreviations: EtE, the ethanolic extract of stem bark from Terminalia fagifolia Mart; AgNPEtE, silver nanoparticles formed with the ethanolic extract of stem bark from Terminalia fagifolia Mart; AqF, the aqueous fraction of the ethanolic extract of stem bark from Terminalia fagifolia Mart; AgNPAqF, silver nanoparticles formed with the aqueous fraction of the ethanolic extract of stem bark from Terminalia fagifolia Mart; ROS, reactive oxygen species ⁎ Corresponding author at: Universidade de Brasília, UNB, Area of Morphology, Faculty of Medicine, FM, CampusDarcy Ribeiro, Asa Norte, University of Brasilia (UnB), 70910900, Brazil. E-mail addresses: jrsaleite@gmail.com, jrleite@pq.cnpq.br (J.R. de Souza de A. Leite).