Fungal growth inhibitory properties of new phytosphingolipid analogues

Abstract

[Aims] To study the growth inhibitory properties of a series of phytosphingosine (PHS) and phytoceramide (PHC) analogues.

[Methods and Results] A panel of two yeast (Candida albicans and Saccharomyces cerevisiae) and six moulds (Aspergillus repens, Aspergillus niger, Penicillium chrysogenum, Cladosporium cladosporioides, Arthroderma uncinatum and Penicillium funiculosum) has been used in this study. A series of new PHS and PHC analogues differing at the sphingoid backbone and the functional group at C1 position were synthesized.

[Conclusions] Among PHS analogues, 1-azido derivative 1c, bearing the natural d-ribo stereochemistry, showed a promising growth inhibitory profile. Among PHC analogues, compound 12, with a bulky N-pivaloyl group and a Z double bond at C3 position of the sphingoid chain, was the most active growth inhibitor. Minimal inhibitory concentration values were in the range of 23–48 μmol l-1 for 1c and 44–87 μmol l-1 for 12.

[Significance and Impact of the Study] Only scattered data on the antifungal activity of phytosphingolipids have been reported in the literature. This is the first time that a series of analogues of this kind are tested and compared to discern their structural requirements for antifungal activity.