ARS | Publication request: Fungicidal Activities of Dihydroferulic Acid Alkyl Ester Analogues

Submitted to: American Society of Pharmacognosy
Publication Type: Abstract Only
Publication Acceptance Date: May 26, 2007
Publication Date: July 14, 2007
Citation: Beck, J.J., Kim, J.H., Campbell, B.C., Chou, S. 2007. Fungicidal Activities of Dihydroferulic Acid Alkyl Ester Analogues. American Society of Pharmacognosy. Meeting Abstract.

Interpretive Summary: Dihydroferulic acid (DFA) is a phenolic metabolite of several plants and is known to possess antioxidant/radical-scavenging properties. To our knowledge it has not yet been reported as an antimicrobial. Previous unreported research demonstrated DFA to possess weak inhibitory activity against the fungi Aspergillus niger and Candida kefyr, in addition to the bacteria Bacillus subtilis and Staphylococcus aureus. This unreported observation, combined with the recent report that the structurally similar ketone derivative vanillylacetone possessed activity against the fungi Saccharomyces cerevisiae and A. flavus, inspired our investigation of ester analogs of DFA for their antifungal capacities. The DFA methyl, ethyl, propyl, hexyl, octyl, and decyl esters were synthesized and examined for antifungal activity. Test fungi included Saccharomyces cerevisiae (wild type, and deletion mutants slt2delta and bck1delta), Aspergillus fumigatus, and A. flavus. Growth inhibition of S. cerevisiae treated with 5 mM of DFA or the corresponding esters was methyl, ethyl, and propyl >98%; hexyl 18.8%; DFA 6.4%; octyl 6.2%; and decyl 2.8%, relative to the control. The 50% minimum inhibitory concentrations for the more potent propyl, methyl, and ethyl esters were 1.5, 2.1, and 4.0 mM, respectively. The propyl ester inhibited 100% growth of both aspergilli at 6.4 mM. The antifungal activity of the DFA analogs appears to result from inducing cellular oxidative stress.

Technical Abstract: The natural product dihydroferulic acid (DFA, 1) and the synthesized DFA methyl (4a), ethyl (4b), propyl (4c), hexyl (4d), octyl (4e), and decyl (4f) esters were examined for antifungal activity. Test fungi included Saccharomyces cerevisiae (wild type, and deletion mutants slt2delta and bck1delta), Aspergillus fumigatus, and A. flavus. Growth inhibition of S. cerevisiae treated with 5 mM of DFA or the corresponding esters was 4a, 4b, and 4c >98%; 4d 18.8%; 1 6.4%; 4e 6.2%; and 4f 2.8%, relative to the control. The 50% minimum inhibitory concentrations for the more active propyl, methyl, and ethyl esters were 1.5, 2.1, and 4.0 mM, respectively. Compound 4c inhibited 100% growth of both aspergilli at 6.4 mM.