Table 2.
Summary of immunosuppressant drugs with antifungal activity
| Immunosuppressants | Fungus | In vitro (MIC: μg/mL) | In vivo | In combination (synergistic effects) | Relevant molecular mechanism | Ref. |
|---|---|---|---|---|---|---|
| Cyclosporine | Aspergillus spp. | 1–25 | - | CAS, ISA | Inhibits the calcineurin pathways. | Marchetti et al. (2000a, 2000b); Kontoyiannis et al. (2003) |
| C. albicans | >10 | Rat | FLC, VRC, CAS, AmB | Inhibits the expression of genes related to hyphal development, adhesion, biofilm formation, and drug transporter in C. albicans (Jia et al. 2016). | Uppuluri et al. (2008); Shinde et al. (2012) | |
| Rhizopus spp., Lichtheimia spp., Mucor spp., Rhizomucor spp. | 1–16 | - | ISA | Schwarz et al. (2019) | ||
| Tacrolimus | Trichosporon asahii | > 64 | - | AmB, CAS | Inhibits the activity of calcineurin pathway. | Kubiça et al. (2016) |
| Aspergillus spp. | 0.25–16 | Mice | CAS | High and Washburn (1997); Steinbach et al. (2004); Kubiça et al. (2016); Schwarz and Dannaoui (2020) | ||
| Fusarium spp. | 1–40 | - | CAS | Shalit et al. (2009) | ||
| C. albicans | No effects. | - | FLC, ITR, VRC | Uppuluri et al. (2008); Sun et al. (2008) | ||
| C. dubliniensis | > 4 | - | CAS, FLC, POS | Zhang et al. (2012) | ||
| Rhizopus spp., Lichtheimia spp., Mucor spp., Rhizomucor spp. | 1–8 | - | ISA | Schwarz et al. (2019) | ||
| Pimecrolimus | Malassezia spp. | 16–64 | - | - | - | Sugita et al. (2006) |
| Rapamycin | C. albicans | < 0.09 - > 100 | - | - | Inhibits the TOR pathways via FKBP12-Rapa complex. | Cruz et al. (2001) |
| C. neoformans | 0.39 - >100 | - | - | Cruz et al. (2001) | ||
| Mucor spp. | 8 | G.mellonella | ISA | Bastidas et al. 2012; Schwarz et al. (2019) | ||
| Rhizopus spp., Lichtheimia spp., Rhizomucor spp. | 8 | ISA | Schwarz et al. (2019) | |||
| Phycomyces blakesleeanus | 6.3-200 | - | CAS, ISA | Bastidas et al. (2012) | ||
| Aspergillus spp. | 16 | Mice | ISA | High and Washburn (1997); Kontoyiannis et al. (2003); Schwarz and Dannaoui (2020) | ||
| Mycophenolic acid | C. neoformans | 30 | Nematode | AmB | Disrupts de novo GTP biosynthesis. | Morrow et al. (2012); Banerjee et al. (2014) |
| C. albicans | 0.25 | - | - | Köhler et al. (2005) | ||
| Mizoribine | C. albicans | - | - | - | Disrupt de novo GTP biosynthesis. | Köhler et al. (2005) |
| Dexamethasone | Resistant-azole C. albicans | No effects. | G. mellonella | FLC | Inhibits the drug efflux pump and reduces the activity of extracellular phospholipases. | Sun et al. (2017) |
| Budesonide | Resistant-azole C. albicans | 16- > 128 | G. mellonella | FLC |
(I) Inhibits the function of drug transporters. (II) Reduces the activity of extracellular phospholipases and the formation of biofilm. (III) Promotes apoptosis by the accumulation of ROS. |
Li et al. (2016) |
| Hydrocortisone | A. fumigatus | - | - | ITR | - | Ramondenc et al. (1998) |
Note: VRC, voriconazole; AmB, amphotericin B; FLC, fluconazole; ITR, itraconazole; POS, posaconazole; CAS, caspofungin; ISA, isavuconazole; -, no studies were mentioned in the corresponding references