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

Abstract

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 μg/mL to 512 μg/mL. 128 μg/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.

Screening the pandemic response box identified benzimidazole carbamates, Olorofim and ravuconazole as promising drug candidates for the treatment of eumycetoma

“…In the past, mammalian models have been used for grain formation, but in 2015 we demonstrated that grain formation can occur in the M. mycetomatis infected invertebrate G. mellonella [22,23]. In previous studies as well in this study, we used this G. mellonella grain model to determine if the compounds active against hyphae in vitro can penetrate grains in vivo [10,[22][23][24]. Four compounds, ravuconazole, olorofim, fenbendazole and MMV1782387 were able to significantly prolong larvae survival on day ten.…”

Evaluation of the Antiparasitic and Antifungal Activities of Synthetic Piperlongumine‐Type Cinnamide Derivatives: Booster Effect by Halogen Substituents

“…The MM55 isolate, which is resistant to cinnamaldehyde (minimal inhibitory concentration/MIC = 222 μg/mL), was used for this study. [14] Although none of the compounds did completely inhibit fungal growth at concentrations of 25 μM and 100 μM, some reduction in growth was observed compared to the solvent-treated control. Compound 4 c demonstrated the highest in vitro activity with percentages metabolic activity of 44.1 % and 26.6 %, respectively.…”

“…Natural products from plants are a rich source for the identification and development of new drugs against human infectious diseases caused by protozoa and fungi. [11][12][13][14] Natural ingredients of several Piper plants exhibited promising activities against various pathogenic protozoal parasites such as Leishmania. The amide alkaloids piperine, isolated from black pepper (Piper nigrum), and piperlongumine (also called piplartine), isolated from long pepper (Piper longum) and other Piper species, are prominent examples of antileishmanial compounds from these plants.…”

“…[30,31] In terms of eumycetoma killing cinnamyl derivatives, an oily mixture of cinnamaldehyde with other cinnamoyl and terpenoid derivatives performed especially well, both in vitro and in vivo. [14] Tubulin is a major drug target in antiparasitic and antifungal research and treatment. Benzimidazoles such as carbendazim, mebendazole and albendazole kill parasites and fungi by disrupting the microtubule structures of treated pathogens.…”

“…Natural products from plants are a rich source for the identification and development of new drugs against human infectious diseases caused by protozoa and fungi [11–14] . Natural ingredients of several Piper plants exhibited promising activities against various pathogenic protozoal parasites such as Leishmania .…”