A new <i>N</i>-acylhydrazone oxadiazole derivative with activity against mycobacteria

<b>Aim:</b> To evaluate the anti<i>-Mycobacterium tuberculosis</i> (<i>Mtb</i>) potential of the hybrid oxadiazol-4-methoxynaphthalene (<b>6n</b>) derived from <i>N</i>-acylhydrazone (<b>4k</b>). <b>Materials &amp; methods:</b> The study determined the minimal inhibitory concentration of (<b>6n)</b> against <i>Mtb</i> H₃₇Rv and <i>Mtb</i> clinical isolates, potential combination of (<b>6n)</b> with anti-tuberculosis drugs and carried out time kill curve assay of <i>Mtb</i> H₃₇Rv. Additional contribution for the analysis of <b>(6n)</b> was explored by <i>in silico</i> pharmacokinetics, and <i>in vitro</i> and <i>in vivo</i> cytotoxicity determinations. <b>Results:</b> The newly synthesized molecule (<b>6n)</b> demonstrated anti-<i>Mtb</i> activity, low cytotoxicity and selectivity for <i>Mtb.</i> <b>Conclusion:</b> The derivative (<b>6n</b>) emerges as a potential anti-TB drug candidate. Tuberculosis (TB) is recognized as a disease strongly influenced by social determination, with a direct relationship with poverty and social exclusion. The investigation of new alternative drugs to overcome resistance in <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) is becoming increasingly necessary to establish safer, more effective and lower-cost therapies, especially against resistant TB. The study compared the <i>in vitro</i> activities of <b>(4k)</b> and (<b>6n)</b> against <i>Mtb</i> H₃₇Rv and <i>Mtb</i> clinical isolates. The derivation of N-acylhydrazone (<b>4k</b>) into 1,3,4-oxadiazole (<b>6n</b>) demonstrated promising outcomes, including enhanced anti-<i>Mtb</i> activity, against multidrug-resistant clinical isolates, low cytotoxicity and selectivity for <i>Mtb.</i> The new molecule (<b>6n</b>) showed promising results against <i>Mtb</i>, including multidrug-resistant isolates. The derivative (<b>6n</b>) emerges as scaffold for future anti-TB drug candidates.