Short communication Antiviral activity of Faramea bahiensis leaves on dengue virus type-2 and characterization of a new antiviral flavanone glycoside $ Adriana C. Nascimento a , Ligia M.M. Valente a, *, Mário Gomes b , Rodolfo S. Barboza a , Thiago Wolff a , Rômulo L.S. Neris c , Camila M. Figueiredo c , Iranaia Assunção-Miranda c, * a Instituto de Química, Universidade Federal do Rio de Janeiro, Av. Athos da Silveira Ramos 149, Centro de Tecnologia, Bl. A, Cidade Universitária, 21941-909, Rio de Janeiro, RJ, Brazil b Instituto de Pesquisas Jardim Botânico do Rio de Janeiro, R. Jardim Botânico 1008, 22470-180, Rio de Janeiro, RJ, Brazil c Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373, Centro de Ciências da Saúde, Bl. I, Cidade Universitária, 21941-970, Rio de Janeiro, RJ, Brazil A R T I C L E I N F O Article history: Received 29 September 2016 Received in revised form 8 January 2017 Accepted 25 January 2017 Available online xxx Keywords: Faramea bahiensis Rubiaceae Flavanone Anti-dengue Antiviral Dengue virus A B S T R A C T Dengue virus infection is a neglected disease prevalent in most tropical and subtropical areas. Currently there is no any antiviral drug indicated for the routine treatment of dengue patients. As part of our ongoing search for potential anti-dengue virus agents we have investigated the methanol extract of Faramea bahiensis (Rubiaceae) leaves. This species is endemic in Brazil, and there are no reports on its chemical composition or therapeutic potential. Its crude MeOH extract showed in vitro non-cytotoxicity and anti-dengue virus serotype 2 (DENV-2) activity in human hepatocarcinoma cell lineage (HepG2). A marked reduction on viral load (100%) was observed. Sequential fractionation of the bioactive crude extract led to the isolation of a bioactive new flavanone glycoside: 5-hydroxy-4 0 -methoxy-flavanone-7- O-ß-D-apiofuranosyl-(1 !6)-ß-D-glucopyranoside, the known 5,4 0 -dihydroxy-flavanone-7-O-ß-D-apio- furanosyl-(1 !6)-ß-D-glucopyranoside and a diateroisomeric epimer pair of the known 5,3 0 ,5 0 - trihydroxy-flavanone-7-O-ß-D-glucopyranoside. The treatment of DENV-2 infected HepG2 cells with the new flavanone was able to control viral replication promoting a reduction of the number of infected cells (12%), together with a decrease of infectious particles in the culture supernatant (97%) and of the number of RNA copies of DENV-2 in HepG2 cells (67%). Structural determinations were made by NMR techniques in one and two dimensions ( 1 H NMR, 13 C NMR, COSY, HSQC and HMBC), HRMS, UV, OR and CD. © 2017 Phytochemical Society of Europe. Published by Elsevier Ltd. All rights reserved. 1. Introduction Dengue fever is a mosquito-borne viral neglected disease prevalent in most tropical and subtropical areas and its incidence has dramatically increased in the last decades (WHO, Updated in 2016). According to the World Health Organization (WHO), only in the Americas in 2015 2.35 million cases were reported, of which 10,200 were diagnosed as the severe form of the disease (also known as dengue hemorrhagic fever), causing around 1000 deaths (WHO, Updated in 2016). In Brazil, it is placed among one of the most serious public health issues registering about 1.6 million cases in 2015 (Brazilian-Health-Ministry, 2016). The dengue symptoms usually start with high fever that can be accompanied by severe headache, retro-orbital pain, muscle and joint pains, nausea, vomiting, swollen glands or rash. In severe cases, vascular permeability leading to hypotension may evolve to shock and hemorrhagic manifestations may occur as well. Currently there is no drug indicated for the routine treatment of dengue patients. Thus, the discovery of drugs that can exert antiviral action against dengue virus (DENV), inhibiting the virus replication cycle without being toxic to the host cell and thus mitigating the symptoms, is highly desirable. The genus Faramea Aubl. (Rubiaceae) is native, but non- endemic to Brazil and contains species in form of shrubs, sub- shrubs or trees. Despite the diversity of the species, few reports can be found on their chemical composition and on their pharmaco- logical potential. Previous phytochemical investigations of Far- amea species have resulted in the isolation and/or characterization of anthraquinones and naphthopyrans (Ferrari et al., 1985), flavans $ Faramea bahiensis was formerly identified as Faramea marambaiae. * Corresponding authors. E-mail addresses: valente@iq.ufrj.br (L.M.M. Valente), iranaiamiranda@micro.ufrj.br (I. Assunção-Miranda). http://dx.doi.org/10.1016/j.phytol.2017.01.013 1874-3900/© 2017 Phytochemical Society of Europe. Published by Elsevier Ltd. All rights reserved. Phytochemistry Letters 19 (2017) 220–225 Contents lists available at ScienceDirect Phytochemistry Letters journal homepa ge: www.elsev ier.com/locate/phytol