Subscribe to RSS
DOI: 10.1055/s-2002-20049
© Georg Thieme Verlag Stuttgart · New York
Natural Products Inhibiting Candida albicans Secreted Aspartic Proteases from Tovomita krukovii
Publication History
January 19, 2001
May 13, 2001
Publication Date:
31 January 2002 (online)
Abstract
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 μg/ml, 25 μg/ml, 40 μg/ml, and 6.5 μg/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).
Key words
Tovomita krukovii - Guttiferae - xanthones - prenylated benzophenone - betulinic acid - SAP inhibitors - antimicrobial activity
References
- 1 Hoegl L, Ollert M, Korting H C. The role of Candida albicans secreted aspartic proteinase in the development of candidoses. Journal Molecular Medicine. 1996; 74 135-42
- 2 Hoegl L, Korting H C, Klebe G. Inhibitors of aspartic proteases in human diseases; molecular modeling comes of age. Pharmazie. 1999; 54 319-29
- 3 Schultes R E. In Botanical museum leaflets. New York; Harvard University Press 1983: 29
- 4 Seo E .-K, Wall M E, Wani M C, Navarro H, Mukherjee R, Farnsworth N R. Cytotoxic constituents from the roots of Tovomita brevistaminea . Phytochemistry. 1983; 52 669-74
- 5 Garcia-Cortez D A, Young M CM, Marston A, Wolfender J L, Hostettmann K. Xanthones, triterpenes and a biphenyl from Kielmeyera coriacea . Phytochemistry. 1998; 47 1367-74
- 6 Jackson B, Locksley H D, Scheinmann F. Extractives from Guttiferae. Part v. Scriblitifolic acid, a new xanthone from Calophyllum scriblitifolium Henderson and Wyatt-Smith. Journal Chemical Society (C). 1967; 22 785-99
- 7 Rocha L, Marston A, Kaplan M AC, Stoeckli-Evans H, Thull U, Testa B, et al. An antifungal γ-pyrone and xanthones with monoamine oxidase inhibitory activity from Hypericum brasiliense . Phytochemistry. 1994; 36 1381-5
- 8 Jackson B, Locksley H D, Moore I, Scheinmann F. Extractives from Guttiferae. Part IX. The isolation of buchanaxanthone and two related xanthones from Garcinia buchananii Baker. Journal Chemical Society (C) 1968: 2579-83
- 9 Locksley H D, Murray I G. Extractives from Guttiferae. Part XIX. The isolation and structure of two benzophenones, six xanthones and two biflavonoids from the Heartwood of Allanblackia floribunda Oliver. Journal of Chemical Society (C). 1971; 1332-40
- 10 Frahm A W, Chaudhuri R K. 13C NMR spectroscopy of substituted xanthones-II 13C NMR spectral study of polyhydroxyxanthones. Tetrahedron. 1979; 35 2035-8
- 11 Ghosal S, Chaudhuri R K, Nath A. Chemical constituents of Gentianaceae IV: New xanthones of Canscora decussata . Jounal of Pharmaceutical Sciences. 1973; 62 137-8
- 12 Wolfender J L, Hamburger M, Msonthi J D, Hostettmann K. Xanthones from Chironia krebsii . Phytochemistry. 1991; 30 3625-29
- 13 Kitanov G, Achtardjiev C. Isolierung von Gentisein aus Hypericum degenii Bornm. Pharmazie. 1979; 34 447-8
- 14 Atkinson J E, Gupta P, Lewis J R. Some phenolic constituents of Gentiana lutea . Tetrahedron. 1968; 24 1507-11
- 15 Ikuta A, Itokawa H. Triterpenoids of Paeonia japonica callus tissue. Phytochemistry. 1988; 27 2813-5
- 16 Zhang Z Z, Koike K, Guo D A, Li C L, Zheng Z H, Jia Z H, . et al . Studies on the chemical constituents of Yunnan wintergreen root Gaultheria yunnanensis (II). Zhongcaoyao. 1999; 30 167-9
- 17 Capobianco J O, Lerner C G, Goldman R C. Application of a fluorogenic substrate in the assay of proteolytic activity and in the discovery of a potent inhibitor of Candida albicans aspartic proteinase. Analytical Biochemistry. 1992; 204 96-102
-
18 National Committee for Clinical Laboratory Standards 1 997. Methods for Dilution Antimicrobial Susceptibility Test for Bacteria that Grow Aerobically. Approved Standard M7-A4, vol. 17, #2. National Committee for Clinical Laboratory Standards Wayne, PA; 4th ed
- 19 Li X C, ElSohly H N, Nimrod A C, Clark A M. Antifungal jujubogenin saponins from Colubrina retusa . Journal of Natural Products. 1999; 62 674-7
- 20 Bohlmann F, Zdero C. Neue Geranylphloroglucin-Derivate aus Helichrysum monticola . Phytochemistry. 1980; 19 683-4
- 21 Hostettmann K, Hostettmann M. Xanthones. Methods in Plant Biochemistry. In: Harborne JB, editor vol. 1 London; Academic Press 1989: 493-508
- 22 Waterman P G, Hussain R A. Major xanthones from Garcinia quadrifaria and Garcinia staudtii stem barks. Phytochemistry. 1982; 21 2099-101
- 23 Miura I, Hostettmann K, Nakanishi K. Carbon-13 NMR of naturally occurring xanthone aglycones and glycosides. Nouveau Journal de Chimie. 1978; 2 653-7
Dr. Hala N. ElSohly
National Center for Natural Products Research
School of Pharmacy
University of Mississippi
University
MS 38677
USA
Email: helsohly@olemiss.edu
Fax: +1 662-915-7989