Evaluation of inhibitory potential of L. amazonensis efflux pumps by furoxan derivative 14e

• Grant number: 15/17911-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2016
• End date: July 31, 2017
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Marcia Aparecida Silva Graminha
• Grantee: Jéssica Naiara Varonez da Fonseca
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

A novel series of furoxan have been recently synthesized, characterized, and evaluated for in vitro activity against promastigote and intracellular amastigote forms of Leishmania amazonensis. The furoxan derivatives exhibited the ability to generate nitric oxide at different levels (7.8% to 27.4%) and showed remarkable leishmanicidal activity against both promastigote and intracellular amastigote forms. The main goal of this proposal is to evaluate the hypothesis that 14e is able to inhibit efflux pumps in L. amazonenensis through flow cytometry using promastigotes cells (wild type and resistant to 14e) stained with rhodamine 123, a well-known substrate for efflux pumps. If 14e is able to inhibit these membrane proteins, we expect the accumulation in cells of rhodamine123. We will also evaluate the ability of 14e to improve the antileishmanial activity of amphotericin B (check board analysis).