A New 1,2-Benzisoxazolin-3-one Synthetized from Eugenol Shows Anti- Candida Spp. Activity, Specially Against Opportunistic Candida Glabrata

Title:A New 1,2-Benzisoxazolin-3-one Synthetized from Eugenol Shows Anti- Candida Spp. Activity, Specially Against Opportunistic Candida Glabrata

Volume: 17 Issue: 5

Author(s): Antonio M. Fregnan, Antonio A. Fernandes Júnior, Dalila J. Alvarenga, Josidel C. Oliver, Naiara C. Silva, Luiz F.L. Coelho, Amanda L. Tranches Dias, Danielle F. Dias, Thiago B. de Souza and Diogo T. Carvalho*

Affiliation:

• Departamento de Alimentos e Medicamentos, Faculdade de Ciencias Farmaceuticas, Universidade Federal de Alfenas, Alfenas,Brazil

Keywords: 1, 2-benzisoxazolin-3-ones, eugenol, molecular hybridization, Candida spp., antifungals, MTT method.

Abstract:

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.

Cite this article as:

Fregnan M. Antonio , Júnior A. Fernandes Antonio , Alvarenga J. Dalila , Oliver C. Josidel , Silva C. Naiara , Coelho F.L. Luiz , Dias L. Tranches Amanda , Dias F. Danielle, de Souza B. Thiago and Carvalho T. Diogo*, A New 1,2-Benzisoxazolin-3-one Synthetized from Eugenol Shows Anti- Candida Spp. Activity, Specially Against Opportunistic Candida Glabrata, Current Bioactive Compounds 2021; 17 (5) : e010621184056 . https://dx.doi.org/10.2174/1573407216999200723114241