Abstract
We evaluated the antifungal activity of benzylidene-carbonyl compounds (LINS03) based on the structure of gibbilimbol from Piper malacophyllum Linn. Five analogues (1–5) were synthetized following a classic aldol condensation between an aromatic aldehyde and a ketone, under basic conditions. These were tested against itraconazole-susceptible (n = 3) and itraconazole-resistant (n = 5) isolates of Sporothrix brasiliensis by M38-A2 guidelines of CLSI. All of them were fungistatic (MIC ranged of 0.11–0.22 mg/mL (1); 0.08–0.17 mg/mL (2); 0.05–0.1 mg/mL (3); 0.04–0.33 mg/mL (4); and 0.04–0.3 mg/mL (5)), highlighting compounds 2 and 3. As fungicidal, compounds 1 and 2 were highlighted (MFC ranged of 0.22–0.89 mg/mL and 0.08–1.35 mg/mL, respectively), compared with the remaining (0.77–> 3.08 mg/mL (3); 0.08–> 2.6 mg/mL (4); and 0.59–> 2.37 mg/mL (5)). The inhibitory activity was related to the benzylidene-carbonyl, whereas the phenol group and the low chain homolog seems to contribute to some extent to the fungicidal effect. Compound 2 highlighted due to the considerable fungistatic and fungicidal activities, including itraconazole-resistant Sporothrix brasiliensis. These findings support the potential usefulness of benzylidene-carbonyl compounds as promising prototypes for the development of antifungal against sporotrichosis by Sporothrix brasiliensis, including against itraconazole-resistant isolates.
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Acknowledgments
The authors also thank Prof. Dr. Zoilo Pires de Camargo (Federal University of São Paulo, UNIFESP, Brazil) for the molecular analysis.
Funding
The authors are grateful to CAPES (financial code 001), CNPq (Grant 306355/2018-3), and FAPERGS and FAPESP (under Grants 2016/25028-3 and 2018/03918-2) for financial support and research scholarships.
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SBW performed the study design, development and methodology, the collection of all data, and the data analysis/interpretation, and wrote all the manuscript. MBC performed the study design, collection of data, data analysis, and the revision of the manuscript. MKR worked in the development and methodology of the antifungal tests and the collection of data. MCAM analyzed the data and revised the manuscript. MTV performed the development and methodology and the collection of data, the data analysis, and interpretation, as well as wrote a section of the manuscript (synthesis of the compounds) and helped in the manuscript revision. JPSF performed the study design, development and methodology, and the collection of data, as well as the data analysis/interpretation and the revision of the manuscript.
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Waller, S.B., Cleff, M.B., Ripoll, M.K. et al. Benzylidene-carbonyl compounds are active against itraconazole-susceptible and itraconazole-resistant Sporothrix brasiliensis. Folia Microbiol 65, 1033–1038 (2020). https://doi.org/10.1007/s12223-020-00814-4
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DOI: https://doi.org/10.1007/s12223-020-00814-4