In vitro and in silico analysis reveals antifungal activity and potential targets of curcumin on Paracoccidioides spp

Braz J Microbiol. 2021 Dec;52(4):1897-1911. doi: 10.1007/s42770-021-00548-6. Epub 2021 Jul 29.

Abstract

The search for new compounds with activity against Paracoccidioides, etiologic agents of Paracoccidioidomycosis (PCM), is extremely necessary due to the current scenario of the available therapeutic arsenal. Treatment is restricted to three classes of antifungals with side effects. Curcumin is a polyphenol with antifungal effects that is extracted from Curcuma longa. The present work aimed to evaluate the activity of curcumin in different species of Paracoccidioides and to evaluate the potential molecular targets of curcumin using computational strategies. In addition, interactions with classic antifungals used in the treatment of PCM were evaluated. Curcumin inhibits the growth of Paracoccidioides spp. exerting a fungicidal effect. The combination of curcumin with amphotericin B, co-trimoxazole, and itraconazole showed a synergistic or additive interaction. Molecular targets as superoxide dismutase, catalase, and isocitrate lyase were proposed based on in silico approaches. Curcumin affects the fungal plasma membrane and increases the production of reactive oxygen species. Therefore, curcumin is a good alternative for the treatment of PCM.

Keywords: Antifungal activity; Curcumin; Paracoccidioides spp..

MeSH terms

  • Antifungal Agents / pharmacology
  • Computer Simulation
  • Curcumin* / pharmacology
  • Curcumin* / therapeutic use
  • Drug Synergism
  • Humans
  • In Vitro Techniques
  • Paracoccidioides* / drug effects
  • Paracoccidioidomycosis* / drug therapy
  • Paracoccidioidomycosis* / microbiology

Substances

  • Antifungal Agents
  • Curcumin