Amlodipine and lufenuron as repurposing drugs against Sporothrix brasiliensis
Vanice Rodrigues Poester, Jéssica Estefania Dávila Hidalgo, Lara Severo Jardim, Mariana Rodrigues Trápaga, Vanessa Brito de Souza Rabello, Rodrigo Almeida-Paes, Rosely Maria Zancope-Oliveira, Melissa Orzechowski Xavier- General Agricultural and Biological Sciences
- General Biochemistry, Genetics and Molecular Biology
- General Medicine
- General Neuroscience
Background
Sporotrichosis caused by Sporothrix brasiliensis is a globally emerging infectious disease with limited therapeutic options. Thus, we aimed to evaluate the in vitro activity of amlodipine (AML) and lufenuron (LUF) alone and their interaction with itraconazole (ITZ), the first-choice drug against S. brasiliensis.
Methods
Twenty clinical isolates of S. brasiliensis from two hyperendemic regions were tested through a microdilution assay to evaluate the minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of AML and LUF. Checkerboard assay was performed with 10 isolates for both drug interactions with ITZ.
Results
AML showed inhibitory and fungicidal activity against all isolates included, with MIC values ranging from 32 to 256 µg/mL, and MFC from 64 to 256 µg/mL. However, none of the S. brasiliensis isolates were inhibited by the highest soluble concentration of LUF (MIC >64 µg/mL for all strains). Synergic interaction of AML and LUF with ITZ occurred in 50% and 40% of the isolates tested, without any antagonistic effects.
Conclusion
Both repurposing drugs evaluated in our study showed a promising in vitro activity, especially in synergy with ITZ against S. brasiliensis, warranting future in vivo investigations regarding its activity.