Anti-Sporothrix activity of ibuprofen combined with antifungal

Abstract

The in vitro activity of ibuprofen, a nonsteroidal anti-inflammatory drug, was evaluated against Sporothrix brasiliensis and S. schenckii, either alone or in combination with amphotericin B, itraconazole, or terbinafine. The inhibitory activity of ibuprofen as a single agent was determined according to minimum inhibitory concentration (MIC) values, while the effect of ibuprofen combined with amphotericin B, itraconazole, or terbinafine was estimated by microdilution checkerboard methodology. The ultrastructural alterations of S. schenckii after exposure to the combination of ibuprofen and amphotericin B were evaluated by scanning electron microscopy (SEM) and flow cytometry analysis. As a single agent, ibuprofen inhibited Sporothrix growth with a MIC median of 256 μg/mL, while the MIC medians of ibuprofen in combination with antifungals were 16 μg/mL and 128 μg/ mL. The MIC values of amphotericin B, itraconazole, and terbinafine were reduced when isolates were co-incubated with ibuprofen, mainly the polyene. The major alteration after treatment with the ibuprofen/amphotericin B combination was the increase in the presence of filamentous forms and high membrane damage with loss of plasma membrane integrity. In summary, we demonstrated that ibuprofen increases the in vitro activity of antifungals, mainly amphotericin B, against S. brasiliensis and S. schenckii. Future in vivo studies exploring combination therapy with ibuprofen and antifungals in animal models are needed to confirm its efficacy.

Drug repurposing strategies in the development of potential antifungal agents

“…In addition, aspirin and ibuprofen combined with fluconazole, caspofungin, and amphotericin B have effects on fungi (Ogundeji et al 2016 ; Yang et al 2016 ). Ibuprofen also has anti- Sporothrix activity singly (median MIC of 256 μg/mL) or in combination with antifungal agents including amphotericin B, itraconazole, and terbinafine (Borba-Santos et al 2021 ). Diclofenac sodium can downregulate the expression of Ef-1 gene, which is involved in cellular RNA transport, cell cycle, and apoptosis (Alves et al 2015 ), thus resulting in a reduction in the formation of A. fumigatus filaments (Nargesi and Rezaie 2018 ).…”

Sporothrix brasiliensis: Epidemiology, Therapy, and Recent Developments

“…Regarding in vitro activity, 25 articles described the inhibitory activity of 28 drugs against S. brasiliensis (100% fungal-inhibition criterion): 20 chemicals and 8 repurposed drugs [ 48 , 49 , 51 , 53 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 ]. Data about the MIC for each individual drug are shown in Table 1 .…”

“…Thus, new options for sporotrichosis treatment, mainly focusing on S. brasiliensis , are urgent. Various in vitro and in vivo studies have described new potential drugs against this Sporothrix species [ 48 , 49 , 50 ]. Chemical drugs are a promising area for research, with data regarding stability and other pharmacological characteristics of the molecules [ 48 , 49 , 50 , 51 , 52 , 53 ].…”

“…Various in vitro and in vivo studies have described new potential drugs against this Sporothrix species [ 48 , 49 , 50 ]. Chemical drugs are a promising area for research, with data regarding stability and other pharmacological characteristics of the molecules [ 48 , 49 , 50 , 51 , 52 , 53 ]. Repurposing drugs are a great strategy to search for new potential antifungals since their pharmacological characteristics are already known, and they ordinarily have demonstrated activity in in vitro tests against S. brasiliensis [ 51 , 52 ].…”

Special issue on sporotrichosis: challenges to deal with the new emerging pathogenic species

“…In recent years, different studies have demonstrated in vitro activity of some anti-inflammatory components. Borba-Santos et al [5] discuss here the in vitro activity of ibuprofen, a nonsteroidal anti-inflammatory drug, against S. brasiliensis and S. schenckii.…”