Design, synthesis and evaluation anti-T.cruzi activity of 5-nitrofurfurilidenes derivatives based in SAR/QSAR strategies

• Grant number: 15/01018-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): May 01, 2015
• Effective date (End): December 31, 2015
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Leoberto Costa Tavares
• Grantee: Laura Freitas de Andrade
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The design of new drugs effective in the treatment of Chagas disease, caused by Trypanosoma cruzi, have shown great need because there are only two drugs currently in use, the benzinidazol and nifurtimox, the latter being banned in Brazil. Nitro Compounds with anti-cruzi activity have shown promising results thus this work involves a series of substituted 5-nitro-furfurylidene and their substituents are planned based on the Craig diagram varying, in this case, the hydrophobicity and preserving the standard of electronic distribution in order to evaluate the influence of hydrophobicity on anti-T. cruzi activity. For this, the ClogP values of the compounds are calculated through applications like Sybyl. Byobyte Co. The synthesis of compounds will be made from the substituted carboxylic acids that are esterified, followed by hydrazinolysis and reaction of obtaining Schiff bases, is obtained in this way, planned analogs which can be identified by determining the melting range ; 1H NMR and 13C NMR; and CHN elemental analysis. The anti-T. cruzi activity assays be made Y strain opposite in their epimastigote way, by determining the minimum inhibitory concentration of 50% growth, IC50, by absorbance at » = 562 UV / VIS spectrum. SAR / QSAR studies, the compounds will be submitted to evaluation of linear and non-linear trends of correlation between hydrophobicity, CLog P or À of Hansch and anti-T. cruzi activity, IC50. The expectation of this study is to identify qualitatively and quantitatively the influence of hydrophobicity on anti-T. cruzi activity if 5-nitro-furfurylidene analogous to nifuroxazide.