Background: In view of the need of discovering new antifungal agents, the synthesis of
compounds comprising new structural scaffolds is an important approach, since they may act by
new mechanisms of action and overcome resistance issues.
Objective: Synthesis of new 1,2-benzisoxazolin-3-ones inspired in eugenol and ebselen as new antifungal
agents against Candida spp.
Methods: A series of 1,2-benzisoxazolin-3-ones, based on eugenol and analogs, was synthesized
by the cyclization of the respective hydroxamic acids under Mitsunobu conditions. IR, NMR, and
MS spectroscopies characterized the synthesized compounds. The final products were screened for
their antifungal activity against five Candida spp., using microdilution assays and cytotoxicity
against peripheral blood mononuclear cells by the MTT method.
Results: The products were obtained in good yields and the results showed that most of the synthesized
compounds were better antifungal agents than eugenol against the Candida species evaluated
and that the derivative IVd (IC50 53 μmol L-1) showed activity comparable to fluconazole against
C. glabrata. Moreover, IVd showed the best selectivity profile among the synthesized new compounds.
Conclusion: A new 1,2-benzisoxazolin-3-one (IVd) was obtained as a promising candidate for the
development of new antifungal agents based on a new chemical scaffold.