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Anti-HCV activity of Sorfifolin, Pedalitin and their Pearacetylated derivatives

Grant number: 14/05445-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2014
Effective date (End): December 31, 2014
Field of knowledge:Physical Sciences and Mathematics - Chemistry
Principal Investigator:Luis Octávio Regasini
Grantee:Caroline Sprengel Lima
Home Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto, SP, Brazil

Abstract

Hepatitis C is a worldwide problem of public health and it is estimated that around 3% of world population is infected by Hepatitic C virus (HCV). Chronic infection can progress to hepatic cirrhosis and hepatocelular carcinoma and it is currently the major cause of liver transplantation. Current therapy based on pegylated interferon (PEF-IFN) and ribavirin presents low efficacy, severe side effects, intravenous administration, and expensive treatment. This therapeutic profile demonstrates the necessity of developing innovative anti-HCV agents. Flavonoids have showed several pharmacological activities, mainly anti-HCV action. Thus, the current study purposes the isolation of two flavones, pedalitin and sorbifolin from Pterogyne nitens Tul. (Leguminosae) leaves. These compounds exhibit similar chemical structure to ladanein, a flavone from Marrubium peregrinum L. (Lamiaceae), which demonstrated potent antiviral activity against several HCV subtypes. Sorbifolin and pedalitin will be submitted to acetylation reactions, using acetic anhydride and pyridine, furnishing peracetylated derivatives. The cytotoxicity of these flavones and their derivatives will be evaluate against Huh-7 hepatocytes from human hepatocellular carcinoma , which will indicate concentrations to antiviral activity assays. Flavones and derivatives will have their anti-HCV activity evaluated against hepatocytes transfected by subgenomic HCV replicons, demonstrating their action against HCV replication. The literature data, describing the anti-HCV activity of flavones structurally similar to sorbifolin and pedalitin, our preliminary phytochemical data, as well as the insertion of this project into FAPESP-GlaxoSmithKline call (Fapesp 2013/50678-3) corroborate to practicability of our purpose.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SHIMIZU, JACQUELINE FARINHA; LIMA, CAROLINE SPRENGEL; PEREIRA, CARINA MACHADO; BITTAR, CINTIA; BATISTA, MARIANA NOGUEIRA; NAZARE, ANA CAROLINA; POLAQUINI, CARLOS ROBERTO; ZOTHNER, CARSTEN; HARRIS, MARK; RAHAL, PAULA; REGASINI, LUIS OCTAVIO; GOMES JARDIM, ANA CAROLINA. Flavonoids from Pterogyne nitens Inhibit Hepatitis C Virus Entry. SCIENTIFIC REPORTS, v. 7, NOV 23 2017. Web of Science Citations: 1.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.