Antifungal agents are drugs that selectively eliminate fungal pathogens from the host with minimal toxicity. Meanwhile, bacteria are prokaryotes and therefore provide many structural and metabolic targets that differ from human hosts. On the contrary, fungi are eukaryotes, so most substances that are toxic to fungi are also toxic to the host. In addition, due to the slow growth of fungi and their presence in multicellular form, they are more difficult to quantify than bacteria. Nonetheless, the occurrence of fungal infection and the evolution of multidrug resistance has increased the demand for new antifungal drugs.

Besides, the target of antifungal drugs must meet several potential criteria. Potential targets must be essential for the survival of fungal cells during static growth, steady-state stability, or host infection processes. Moreover, targeting fungal-specific proteins is also important. Fungal-specific metabolic pathways are attractive targets, as each metabolic component is a potential target. Finally, because the plasma membrane can serve as a barrier for chemicals, cell surface proteins are more suitable as targets. Due to these limitations, the intracellular targets of currently available antifungal drugs are limited to processes related to the cell wall, cell membrane, and ribonucleotide metabolism. Today, we will introduce an orally active anti-inflammatory and antifungal agent, Seselin.

Seselin is an Orally Active Antifungal Agent for Inflammation Research.

To begin with, Seselin is an anticancer, antinociceptive, anti-inflammatory, and antifungal agent. Furthermore, Seselin shows cytotoxic effects with ED₅₀ of 8.66 and 9.94 μg/mL against P-388 and HT-29 cells, respectively.Seselin with 5-20 μM for 0.5-24 h inhibits cytokine output from macrophages stimulated by LPS and IFN-γ dose- and time-dependently. Interestingly, Seselin inhibits the expression of proinflammatory macrophage markers (iNOS, phagocytosis, CD11c) in BMDMs. Additionally, Seselin blocks the STAT1 signaling pathway.

Taken together, Seselin with 0.5-40.5 mg/kg by s.c. once shows peripheral anti-inflammatory and antinociceptive activities in mice. Importantly, Seselin ameliorates sepsis induced by caecal ligation and puncture in mice.

All in all, Seselin is an orally active and potent antifungal agent for inflammation research.

References:

[1] Lima V, et al. Fitoterapia. 2006 Dec;77(7-8):574-8.

[2] Feng L, et al. Br J Pharmacol. 2019 Jan;176(2):317-333.