Isolation, Bromination, and Antimicrobial Activity of 3-Ethyl-4-hydroxy-6-methyl-2H-pyran-2-one from Sea Cucumber-Associated Fungus Trichoderma koningii KMM 4751.

Objectives

This study aimed to isolate secondary metabolites from sea cucumber-associated fungus Trichoderma koningii KMM 4751, obtain their bromine derivatives, and investigate their antimicrobial and cytotoxic activities.

Results

3-Ethyl-4-hydroxy-6-methyl-2H-pyran-2-one (EHMP) was isolated from fungal extract. It was brominated, and a previously unreported 6-(bromomethyl)-3-ethyl-4-hydroxy-2H-pyran-2-one (Br-EHMP) was obtained. EHMP inhibited the formation of Candida albicans biofilms with an IC50 of 49.3 µM, but Br-EHMP was less active. Simultaneously, bromination of EHMP significantly enhanced the inhibitory effect of Br-EHMP on Staphylococcus aureus growth and biofilm formation without increasing cytotoxicity to H9c2 cells. Br-EHMP at 10 μM can inhibit sortase A activity by near 30% in a cell-free assay. In silico molecular docking predicted the interaction of Br-EHMP with Cys184 in the sortase A active site.

Conclusions

Br-EHMP emerges as a promising antibiofilm agent, and its mechanism involves sortase A inhibition.