1 research outputs found
Design, Synthesis, and Characterization of N‑Oxide-Containing Heterocycles with in Vivo Sterilizing Antitubercular Activity
Tuberculosis,
caused by Mycobacterium tuberculosis (<i>Mtb</i>), is the infectious disease responsible for
the highest number of deaths worldwide. Herein, 22 new N-oxide-containing
compounds were synthesized followed by <i>in vitro</i> and <i>in vivo</i> evaluation of their antitubercular potential against <i>Mtb</i>. Compound <b>8</b> was found to be the most promising
compound, with MIC<sub>90</sub> values of 1.10 and 6.62 μM against
active and nonreplicating <i>Mtb</i>, respectively. Additionally,
we carried out <i>in vivo</i> experiments to confirm the
safety and efficacy of compound <b>8</b>; the compound was found
to be orally bioavailable and highly effective, leading to a reduction
of <i>Mtb</i> to undetectable levels in a mouse model of
infection. Microarray-based initial studies on the mechanism of action
suggest that compound <b>8</b> blocks translation.
Altogether, these results indicate that benzofuroxan derivative <b>8</b> is a promising lead compound for the development of a novel
chemical class of antitubercular drugs