The synthetic synergistic cinnamon oil CIN-102 is active against Madurella mycetomatis, the most common causative agent of mycetoma

Mycetoma is a devastating neglected tropical infection of the subcutaneous tissue and most commonly caused by the fungus Madurella mycetomatis. Treatment of mycetoma consists of a combination of a long term antifungal treatment with itraconazole and surgery. However, treatment is associated with low success rates. Therefore, there is a need to identify novel treatments for mycetoma. CIN-102 is a synthetic partial copy of cinnamon oils with activity against many pathogenic bacteria and fungi. In this study we determined the in vitro activity of CIN-102 against 21 M. mycetomatis isolates and its in vivo efficacy in a M. mycetomatis infected Galleria mellonella larval model. In vitro, CIN-102 was active against M. mycetomatis with MICs ranging from 32 mu g/mL to 512 mu g/mL. 128 mu g/mL was needed to inhibit the growth in 50% of tested isolated. In vivo, concentrations below the MIC of 40 mg/kg and 80 mg/kg CIN-102 prolonged larval survival, but higher concentrations of CIN-102 did not. Author summary Mycetoma is a tropical infection causing large tumorous lesions on mainly the foot. This infection is most commonly caused by the fungus Madurella mycetomatis. Mycetoma is treated with antifungal agents and surgery but with low success rates. In our search for novel treatments for mycetoma we determined if CIN-102, a synthetic oil that resembles cinnamon oil, would be therapeutic in mycetoma. We therefore first determined the activity of this oil against the fungus in vitro. We found that CIN-102 could inhibit M. mycetomatis growth in vitro. To determine if CIN-102 was also active against the mycetoma grain in vivo, we determined the efficacy in our Galleria mellonella grain model. Interestingly, CIN-102 was found to be effective in the larvae at a low concentrations.

Automated summary

Mycetoma, caused by Madurella mycetomatis, is a challenging tropical infection with low treatment success rates. CIN-102, a synthetic oil resembling cinnamon oil, showed promising in vitro activity against M. mycetomatis and efficacy in reducing larval mortality in an infected model.