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

PLoS Negl Trop Dis. 2021 Jun 9;15(6):e0009488. doi: 10.1371/journal.pntd.0009488. eCollection 2021 Jun.

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 isolates. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology*
  • Benzoates / chemical synthesis
  • Benzoates / pharmacology*
  • Cinnamates / chemical synthesis
  • Cinnamates / pharmacology*
  • Cinnamomum zeylanicum / chemistry*
  • Drug Combinations
  • Drug Synergism
  • Humans
  • Larva / drug effects
  • Larva / growth & development
  • Madurella / drug effects*
  • Madurella / genetics
  • Madurella / growth & development
  • Microbial Sensitivity Tests
  • Moths / microbiology
  • Mycetoma / drug therapy
  • Mycetoma / microbiology*
  • Terpenes / chemical synthesis
  • Terpenes / pharmacology*

Substances

  • Antifungal Agents
  • Benzoates
  • CIN-102
  • Cinnamates
  • Drug Combinations
  • Terpenes

Grants and funding

This study was supported by Septeos. The funders had no role in study design, data collection and analysis, nor the decision to publish.