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)-beta-D-glucopyranoside (11). On the basis of spectroscopic analysis, the structures of 1-10 were established as 3beta,14alpha,15alpha,21beta,29-pentahydroxyserratane-24-oic acid (lycernuic acid C, 1), 3beta,14alpha,15alpha,21beta-tetrahydroxyserratane-24-oic acid (lycernuic acid D, 2), 3beta,14beta,21beta-trihydroxyserratane-24-oic acid (lycernuic acid E, 3), 3beta,21beta,29-trihydroxy-16-oxoserrat-14-en-24-methyl ester (lycernuic ketone A, 4), 3alpha,21beta,29-trihydroxy-16-oxoserrat-14-en-24-methyl ester (lycernuic ketone B, 5), 3alpha,21beta,24-trihydroxyserrat-14-en-16-one (lycernuic ketone C, 6), 3beta,21beta-dihydroxyserrat-14-en-24-oic acid (lycernuic acid A, 7), 3beta,21beta,29-trihydroxyserrat-14-en-24-oic acid (lycernuic acid B, 8), serrat-14-en-3beta,21beta-diol (9), and serrat-14-en-3beta,21alpha-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 microg/mL, respectively, while the other compounds were inactive.
Zhang
Zhizhen
Z
National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, Department of Pharmacognosy, The University of Mississippi, University, Mississippi 38677, USA.
ElSohly
Hala N
HN
Jacob
Melissa R
MR
Pasco
David S
DS
Walker
Larry A
LA
Clark
Alice M
AM
D000107:Acetylation; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D002176:Candida albicans / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006868:Hydrolysis; D020128:Inhibitory Concentration 50; D029542:Lycopodiaceae / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010568:Peru; D010946:Plants, Medicinal / Q000737:chemistry*; D011480:Protease Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D011480:Protease Inhibitors; D014315:Triterpenes; D016282:Aspartic Acid Endopeptidases