title: Antifungal activity of cinnamic acid derivatives involves inhibition of benzoate 4-hydroxylase (CYP53).
abstract: OBJECTIVE
  CYP53A15, from the sorghum pathogen Cochliobolus lunatus, is involved in detoxification of benzoate, a key intermediate in aromatic compound metabolism in fungi. Because this enzyme is unique to fungi, it is a promising drug target in fungal pathogens of other eukaryotes.
  
  
  RESULTS
  In our work, we showed high antifungal activity of seven cinnamic acid derivatives against C. lunatus and two other fungi, Aspergillus niger and Pleurotus ostreatus. To elucidate the mechanism of action of cinnamic acid derivatives with the most potent antifungal properties, we studied the interactions between these compounds and the active site of C. lunatus cytochrome P450, CYP53A15.
  
  
  CONCLUSIONS
  We demonstrated that cinnamic acid and at least four of the 42 tested derivatives inhibit CYP53A15 enzymatic activity.
  
  
  CONCLUSIONS
  By identifying selected derivatives of cinnamic acid as possible antifungal drugs, and CYP53 family enzymes as their targets, we revealed a potential inhibitor-target system for antifungal drug development.
authors: National Institute of Chemistry, Ljubljana, Slovenia.
authors: B
authors: B
authors: Korošec
authors: M
authors: M
authors: Sova
authors: S
authors: S
authors: Turk
authors: N
authors: N
authors: Kraševec
authors: M
authors: M
authors: Novak
authors: L
authors: L
authors: Lah
authors: J
authors: J
authors: Stojan
authors: B
authors: B
authors: Podobnik
authors: S
authors: S
authors: Berne
authors: N
authors: N
authors: Zupanec
authors: M
authors: M
authors: Bunc
authors: S
authors: S
authors: Gobec
authors: R
authors: R
authors: Komel
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001203:Ascomycota / Q000187:drug effects; D050565:Benzoate 4-Monooxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D002934:Cinnamates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005658:Fungi / Q000201:enzymology; D020076:Pleurotus / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D002934:Cinnamates; D004791:Enzyme Inhibitors; C029010:cinnamic acid; D050565:Benzoate 4-Monooxygenase
keywords: CYP53 inhibition; Cochliobolus lunatus; antifungal activity; cytochrome P450, benzoate 4-monooxygenase; potential antifungal drugs