Natural products inhibiting Candida albicans secreted aspartic proteases from Tovomita krukovii.
Assay-guided fractionation of the ethanol extract of Tovomita krukovii resulted in the identification of four new xanthones (1 - 4) and ten known compounds (5 - 14). The structures of compounds 1 - 14 were determined by spectral data to be 3,5-dihydroxy-4-methoxyxanthone (1), 1,3,5,7-tetrahydroxy-8-isoprenylxanthone (2), 1,3,5-trihydroxy-8-isoprenylxanthone (3), 1,5,7-trihydroxy-8-isoprenylxanthone (4), 1,3,7-trihydroxy-2-isoprenylxanthone (5), 1,5-dihydroxyxanthone (6), 1,6-dihydroxy-5-methoxyxanthone (7), 1,3,5-trihydroxyxanthone (8), 1,3,6-trihydroxy-5-methoxyxanthone (9), 1,6-dihydroxy-3,5-dimethoxyxanthone (10), 1,3,7-trihydroxyxanthone (11), 3-geranyl-2,4,6-trihydroxybenzophenone (12), betulinic acid (13), and 3,4-dihydroxybenzoic acid (14). Compounds 2, 3, 12 and 13 showed inhibitory effects against Candida albicans secreted aspartic proteases (SAP) with IC50 values of 15 microg/ml, 25 microg/ml, 40 microg/ml, and 6.5 microg/ml, respectively, while the other compounds were inactive. In addition, compound 12 showed activity against C. albicans, C. neoformans, S. aureus and methicillin resistant S. aureus (MRS).
Zhang
Zhizhen
Z
National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, Thad Cochran Research Center, School of Pharmacy, 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
D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases / Q000187:drug effects / Q000378:metabolism; D002176:Candida albicans / Q000187:drug effects*; D028084:Clusiaceae; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D010434:Pepsin A / Q000187:drug effects / Q000378:metabolism; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D018547:Plant Stems / Q000737:chemistry; D014966:Xanthenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D044004:Xanthones
C452873:3,5-dihydroxy-4-methoxy-xanthone; D000935:Antifungal Agents; D010936:Plant Extracts; D014966:Xanthenes; D044004:Xanthones; D016282:Aspartic Acid Endopeptidases; D010434:Pepsin A