Antifungal activity of cinnamic acid derivatives involves inhibition of benzoate 4-hydroxylase (CYP53)

作者：Korosec B^*; Sova M; Turk S; Krasevec N; Novak M; Lah L; Stojan J; Podobnik B; Berne S; Zupanec N; Bunc M; Gobec S; Komel R

来源：Journal of Applied Microbiology, 2014, 116(4): 955-966.

DOI：10.1111/jam.12417

• potential antifungal drugs
• CYP53 inhibition
• antifungal activity
• Cochliobolus lunatus
• cytochrome P450, benzoate 4-monooxygenase

Aims
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.
Methods and 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.
Conclusion
We demonstrated that cinnamic acid and at least four of the 42 tested derivatives inhibit CYP53A15 enzymatic activity.
Significance and Impact of the Study
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.

• 出版日期2014-4