Quinoxaline 1,4-di-n-oxide and the potential for treating tuberculosis

Abstract

New drugs active against drug-resistant tuberculosis are urgently needed to extend the range of tuberculosis (TB) treatment options to cover drug resistant infections. New anti-TB agents can improve the current chemotherapeutic anti-TB treatment. The properties and the recent developments of quinoxaline 1,4-di-Noxide derivatives as potential anti-TB agents. Some specific agents have excellent anti-TB drug properties, are active on drug resistant strains and non replicating mycobacteria. Various quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives were evaluated as in-vitro anti-TB activity against M. tuberculosis strain. Compounds with a methyl moiety substituted in position 3 and unsubstituted benzyl substituted on the carboxamide group provide an efficient approach for further development of anti-TB agents. The 3-phenylquinoxaline 1,4-di-N-oxide with selective activity against M. tuberculosis have been evaluated. Some compounds showed an MIC value less than 0.2µg/mL, a value on the order of the MIC of rifampicin. The most active and selective compounds carry a fluorine atom in the quinoxaline 7-position or in the phenyl substituent para-position. The potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for synthesizing new analogues, particularly 7-methyl-3-(4’-fluoro) phenyl quinoxaline-2-carbonitrile 1,4-di-N-oxide compound (MIC <0.2 µg/mL and SI >500).