Synthetic molecular mimics of naturally occurring cyclopentenones exhibit antifungal activity towards pathogenic fungi

Abstract

The naturally occurring reactive electrophilic species 12-oxo-phytodienoic acid (12-oxo-PDA) is a potent antifungal agent, whereas the plant growth regulator jasmonic acid, which is synthesized from 12-oxo-PDA, is ineffective. To address what structural features of the molecule endow it with antifungal activity, we synthesized a series of molecular mimics of 12-oxo-PDA varying in the length of the alkyl chain at its C-4 ring position. The octyl analogue (4-octyl cyclopentenone) was the most effective at suppressing spore germination and subsequent mycelial growth of a range of fungal pathogens and was particularly effective against Cladosporium herbarum and Botrytis cinerea, with minimum fungicidal concentrations in the range 100-200 mM. Introduction of a carboxyl group to the end of the chain, mimicking natural fatty acids, markedly reduced antifungal efficacy. Electrolyte leakage, indicative of membrane perturbation, was evident in both C. herbarum and B. cinerea exposed to 4-octyl cyclopentenone. Lipid composition analysis of the fungal spores revealed that those species with a high oil content, namely Fusarium oxysporum and Alternaria brassicicola, were less sensitive to 4-octyl cyclopentenone. The comparable hydrophobicity of 4-octyl cyclopentenone and 12-oxo-PDA accounts for the similar spore suppression activity of these two compounds. The relative ease of synthesis of 4-octyl cyclopentenone makes it an attractive compound for potential use as an antifungal agent.

Jasmonates: biosynthesis, perception and signal transduction

“…However the widespread occurrence of glycolipid bound precursors for JA biosynthesis is questionable and may be restricted to a number of species (17) as they are not detected in other well studied species such as tomato and potato. Interestingly, JA shows little direct antimicrobial activity against a range of common disease-forming fungi and bacteria whereas OPDA is a potent antimicrobial compound which contains an a,b-unsaturated carbonyl group (18). Studies on the structural basis for this have been made and the C8 chain arm combined with a cyclopentene ring was shown to be the most effective molecule in antimicrobial tests (18).…”

“…Interestingly, JA shows little direct antimicrobial activity against a range of common disease-forming fungi and bacteria whereas OPDA is a potent antimicrobial compound which contains an a,b-unsaturated carbonyl group (18). Studies on the structural basis for this have been made and the C8 chain arm combined with a cyclopentene ring was shown to be the most effective molecule in antimicrobial tests (18). OPDA is exported from the chloroplast to the peroxisome and may involve specific transporter proteins (19).…”