Studies in vitro and in vivo of furoxan compounds with potential application for the treatment of tuberculosis

Abstract

Tuberculosis (TB) is an infectious disease caused mainly by the pathogen Mycobacterium tuberculosis (MTB), and is demanding the development of new strategies for its control. The mortality rate of TB has fallen 45% since 1990 and the world is on track to achieve the global target of 50% reduction by 2015. This optimistic scenario is fulfilled in relation to the total number of cases, however a new problem arises: the resistance. A fact proven by the estimated 450,000 new cases of MDR-TB in 2012 and the report of XDR - TB in 92 countries. The search for new drugs aims to improve the condition of the patient's treatment. In view of this problem, in 2013 we launched the proposal grant "Young Researcher - FAPESP" which has just been approved (No. 2013/14957-5). The PhD scholarship requested here is a fundamental part of the project. This project aims to investigate new five furoxan promising compounds. In preliminary studies, we found that these compounds have a high selective toxicity against MTB with extremely high activity with MIC values lower than 1 µg/mL along with low cytotoxicity against two different cell lines (Vero and J774A.1) providing a high select index. On one hand, as one of the mechanisms of escaping immune response, MTB skillfully suppress the pathways involved in the production of nitric oxide (NO) by macrophages. On the other hand, this class of compounds is described in the literature as having the ability to donate NO assisting the pathway that is suppressed during the TB infection. This hypothesis is effectively investigated with the safety of these new molecules in order to propose to the end, new molecules for the treatment of particular cases of TB resistance. (AU)