Design and synthesis of new 1,4-di-N-oxide quinoxaline as antitubercular compounds to treat multi drug-resistant (MDR) and latent tuberculosis

Abstract

Mycobacterium tuberculosis (MTB), the main agent of tuberculosis (TB), is responsible for the annual death of two to three million people worldwide, and global economic damages of about 12 billion dollars by year. Currently, one of the major global concerns is the increasing number of cases of multi drug-resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) due to the high mortality rate, difficulty of treatment and the high costs involved. Compounds containing the N-oxide function such as quinoxalines has been described as prototypes for discovery of novel anti-TB drugs. The quinoxaline 1,4-di-N-oxide are heterocyclic compounds bioreducible and selectively toxic in hypoxic conditions, able to increase oxidative stress by increasing levels of reactive oxygen and nitrogen species and thus cause damage to the invading microorganisms. This class has been described as useful in treating not only the MDR-TB and XDR-TB, but also latent TB. In this context, we will synthesize and characterize the chemical structure of a series of quinoxalines designed by molecular hybridization strategy. These novel compounds will be further evaluated against MTB using H37Rv strains and MDR clinical isolates (genotypically and phenotypically characterized) by the laboratory of mycobacteria from School of Pharmaceutical Sciences, São Paulo State University - Araraquara -SP. (AU)