Synthesis and antimicrobial evaluation of hybrids methoxynaphthalene-<i>N</i>-acylhydrazones/1,3,4-oxadiazoles

Paracoccidioidomycosis is a neglected tropical disease caused by the fungi <i>Paracoccidoides</i> spp. In cases of clinical manifestations involving the lung, its symptoms can be confused with tuberculosis, in addition to the possibility of patients presenting a co-infection between the two. Considering previous studies by our research group evaluating <i>N</i>-acylhydrazones and 1,3,4-oxadiazoles containing the 4-methoxynaphthalene ring, this work proposed the synthesis of new <i>N</i>-acylhydrazones and new 1,3,4-oxadiazoles containing the 2-methoxynaphthalene ring. Starting from the precursor block 2-methoxy-1-naphthaldehyde, <i>N</i>-acylhydrazones and their respective 1,3,4-oxadiazoles containing the 2-methoxynaphthalene ring were synthesized. The antifungal activity was evaluated against <i>P.</i> <i>brasiliensis</i> (<i>P.b</i>.18) and antimycobacterial activity against <i>M.</i> <i>tuberculosis</i> (H₃₇Rv). The antimicrobial activity was tested for nine <i>N</i>-acylhydrazones and four 1,3,4-oxadiazoles in which structures showing anti-<i>P.b</i>. activity, highlighting the <i>N</i>-acylhyadrazone <b>5f</b> and 1,3,4-oxadiazole <b>6f</b> with MIC of 0.48 ug mL⁻¹ and 1.95 ug mL⁻¹, respectively, and substances with anti-<i>M.tb</i>. activity with MIC between 7.8 and 15.6 ug mL⁻¹ (<b>6a</b> and <b>6b</b>, respectively). New structures containing methoxynaphalene rings and phenol or substituted phenol or pyridine groups can be added to the chemolibrary of candidates for prototypes of drugs with antimicrobial activity against <i>P.b</i>.18 and H₃₇Rv.