3-Phenacylideneoxindoles as a New Class of Antifungal Compounds Against Paracoccidioides Spp.

Abstract

Aims: Considering the need to identify new compounds with antifungal action, the activity of five 3-phenacylideneoxindoles compounds was evaluated. Materials & methods: The compounds were synthesized, and their antifungal activity was elucidated through minimum inhibitory concentration tests and interaction assay with other antifungals. Potential targets of compounds were predicted in silico. Results: 3-phenacylideneoxindoles compounds inhibited fungal growth with minimum inhibitory concentration and minimum fungicidal concentration ranging from 3.05 to 12.26 μM. The compounds demonstrated high selectivity index and presented a synergistic effect with itraconazole. In silico prediction revealed the pentafunctional AROM polypeptide, enolase, superoxide dismutase, catalase and kinases as proteins targets of the compound 4a. Conclusion: The results demonstrate that 3-phenacylideneoxindoles is a potential new class of antifungal compounds for paracoccidioidomycosis treatment.

Proteomic Profiling of Paracoccidioides brasiliensis in Response to Phenacylideneoxindol Derivative: Unveiling Molecular Targets and Pathways

“…OPI was synthesized according to the method described by Silva et al [ 10 ]. A solution containing the mixture of 4.1 g (4 mmol) of acetophenone and 3.5 mL (34 mmol) of diethyl amine in 10 mL of ethyl alcohol was added dropwise to a solution of 5.0 g (34 mmol) of isatin in 30 mL of ethyl alcohol, under magnetic stirring at room temperature for 24 h. After this period, the resulting solid was filtered in a Büchner funnel, washed with a cold mixture (1:1) of water/ethyl alcohol, and dried at room temperature, yielding the intermediate 3-hydroxy-3-phenacyloxindole.…”

“…Considering the need to identify new compounds with antifungal activity against PCM, we previously evaluated the activity of five phenacylideneoxindoles compounds against several Paracoccidioides species [ 10 ]. The phenacylideneoxyndoles are nitrogenous heterocyclic compounds with a chemical structure that includes an oxindole ring with a phenacylidene group attached to it.…”

“…In our study with phenacylideneoxindoles [ 10 ], the compound (E)-3-(2-oxo-2-phenylethylidene)indolin-2-one (OPI) exhibited promising antifungal activity, displaying fungicidal effects and synergistic activity with itraconazole. In addition to conducting in vitro experiments, we also performed in silico predictions of potential molecular targets for OPI.…”