Natural Products Inhibiting Candida albicans Secreted Aspartic Proteases from Lycopodium cernuum

Activity-guided fractionation of an ethanol extract of Lycopodium cernuum for Candida albicans secreted aspartic proteases (SAP) inhibition resulted in the identification of six new (1−6) and four known (7−10) serratene triterpenes, along with the known apigenin-4'-O-(2' ',6' '-di-O-p-coumaroyl)-β-d-glucopyranoside (11). On the basis of spectroscopic analysis, the structures of 1−10 were established as 3β,14α,15α,21β,29-pentahydroxyserratane-24-oic acid (lycernuic acid C, 1), 3β,14α,15α,21β-tetrahydroxyserratane-24-oic acid (lycernuic acid D, 2), 3β,14β,21β-trihydroxyserratane-24-oic acid (lycernuic acid E, 3), 3β,21β,29-trihydroxy-16-oxoserrat-14-en-24-methyl ester (lycernuic ketone A, 4), 3α,21β,29-trihydroxy-16-oxoserrat-14-en-24-methyl ester (lycernuic ketone B, 5), 3α,21β,24-trihydroxyserrat-14-en-16-one (lycernuic ketone C, 6), 3β,21β-dihydroxyserrat-14-en-24-oic acid (lycernuic acid A, 7), 3β,21β,29-trihydroxyserrat-14-en-24-oic acid (lycernuic acid B, 8), serrat-14-en-3β,21β-diol (9), and serrat-14-en-3β,21α-diol (10). The 13C NMR data for the known compounds 7 and 8 are reported for the first time. Compounds 1 and 11 showed inhibitory effects against C. albicans secreted aspartic proteases (SAP) with IC50 of 20 and 8.5 μg/mL, respectively, while the other compounds were inactive.