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

甲氧基萘-N-酰基腙/1,3,4-噁二唑杂合物的合成及抗菌活性评价

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Abstract

AIMS: Paracoccidioidomycosis is a neglected tropical disease caused by the fungi Paracoccidoides 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 N-acylhydrazones and 1,3,4-oxadiazoles containing the 4-methoxynaphthalene ring, this work proposed the synthesis of new N-acylhydrazones and new 1,3,4-oxadiazoles containing the 2-methoxynaphthalene ring. MATERIALS & METHODS: Starting from the precursor block 2-methoxy-1-naphthaldehyde, N-acylhydrazones and their respective 1,3,4-oxadiazoles containing the 2-methoxynaphthalene ring were synthesized. The antifungal activity was evaluated against P. brasiliensis (P.b.18) and antimycobacterial activity against M. tuberculosis (H(37)Rv). RESULTS: The antimicrobial activity was tested for nine N-acylhydrazones and four 1,3,4-oxadiazoles in which structures showing anti-P.b. activity, highlighting the N-acylhyadrazone 5f and 1,3,4-oxadiazole 6f with MIC of 0.48 ug mL(-1) and 1.95 ug mL(-1), respectively, and substances with anti-M.tb. activity with MIC between 7.8 and 15.6 ug mL(-1) (6a and 6b, respectively). CONCLUSION: 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 P.b.18 and H(37)Rv.

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