Onychomycosis is an infection of the nail plate that is prevalent among the ageing population. Onychomycosis is difficult to treat with low initial cure rates, high rates of relapse, and reinfection. In this study, researchers determined the antifungal activity of ME1111 against dermatophyte species known to cause onychomycosis. ME1111 is a potent antifungal agent that is active against dermatophytes, has an excellent ability to penetrate human nails, and is being developed as a topical agent for onychomycosis. Especially, ME1111 is a succinate dehydrogenase inhibitor.
ME1111 exerts a strong inhibitory effect on succinate-DCIP reductase activity in T. rubrum (IC50=0.029 μg/mL) and T. mentagrophytes (IC50=0.025 μg/mL). Succinate dehydrogenase (complex II) is the primary target of ME1111. Furthermore, ME1111 possesses potent antifungal activity against dermatophytes, such as Trichophyton rubrum and Trichophyton mentagrophytes. Trichophyton rubrum and Trichophyton mentagrophytes are common causative organisms of onychomycosis. On the other hand, ME1111 demonstrates a relatively weak inhibitory effect on the corresponding enzyme activity in human K562 (IC50=1.4 μg/mL) and HepG2 (IC50=0.94 μg/mL) cells.
ME1111 is a novel selective inhibitor of succinate dehydrogenase (complex II) of dermatophyte species, whose small molecular weight enhances its ability to penetrate the nail plate. In addition, researchers determined the antifungal activity of ME1111 against dermatophyte strains. The MIC90 of ME1111 against dermatophyte strains is 0.25 μg/mL. Additionally, ME1111 is fungicidal at clinically achievable concentrations against dermatophytes, and its MFC90s against Trichophyton rubrum and Trichophyton mentagrophytes are 8 μg/mL.
In conclusion, ME1111 is a potent inhibitor of succinate dehydrogenase (complex II) for onychomycosis.
Takahata S, et al. Mechanism of Action of ME1111, a Novel Antifungal Agent for Topical Treatment of Onychomycosis. Antimicrob Agents Chemother. 2015 Nov 23;60(2):873-80.