The São Paulo State University (UNESP), School of Pharmaceutical Sciences synthesized 22 new N-oxide-containing compounds and evaluated in vitro and in vivo antitubercular potential against M. tuberculosis. Compound 8 was found to be the most promising compound, with MIC90 values of 1.10 and 6.62 μM against active and nonreplicating Mtb, respectively. Studies of cytotoxicity, safety, absorption, distribution, and metabolism of compound 8 support its candidacy. The compound was found to be orally bioavailable and highly effective with a reduction of Mtb to undetectable levels in a mouse model of infection. Microarray-based initial studies on the mechanism of action suggest that compound 8 blocks translation. Altogether, these results indicate that benzofuroxan derivative 8 is a promising lead compound for the development of a novel chemical class of antitubercular drugs.
(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo
(CNPQ) Conselho Nacional de Desenvolvimento Cientifíco e Tecnoloǵico