
Abstract
Sixteen convolvulaceous glycolipids selected from the tricolorin (1 - 7) and orizabin (8 - 16) series, proved to be strong in vitro inhibitors of the enzyme that catalyzes the synthesis of 1,3-β-D-glucan, a major polymer of fungal cell-walls. Results provide an insight into function of the specific structures of these complex macrocyclic lactones as inhibitors of the 1,3-β-D-glucan synthase and open the possibility of using these compounds as starting points for the development of antifungal agents that act by inhibiting fungal cell-wall synthesis.
References
-
1
Ablordeppey S Y, Fan P, Ablordeppey J H, Mardenborough L.
Systemic antifungal agents against AIDS-related opportunistic infections: Current status and emerging drugs in development.
Current Medicinal Chemistry.
1999;
6
1151-95
-
2 Selitrennikoff C P. Screening for antifungal drugs. In: Finkelstein D, Ball C, editors Biotechnology of filamentous fungi. Technology and products. Boston; Butterworth Heinemann 1992: 189-217
-
3 Walsh T J. Invasive fungal infections: Problems and challenges for developing new antifungal agents. In: Sutcliffe J, Georgopapadakou NH, editors Emerging targets in antibacterial and antifungal chemotherapy. New York; Chapman and Hall 1992: 349-73
-
4
Fromtling R A.
Progress in antifungal chemotherapy.
Drug News Perspectives.
1999;
12
557-69
-
5 Selitrennikoff C P. Antifungal drugs: (1,3)-β-D-glucan-synthase inhibitors. Heidelberg; Springer-Verlag 1995: 1-10
-
6
Onishi J, Meinz M, Curotto J, Dreikorn S, Rosenbach M, Douglas C, Abruzzo G, Flattery A, Kong L, Cabello A, Vicente F, Pelaez F, Diez M T, Martin I, Bills G, Giacobbe R, Dombrowski A, Schwartz R, Morris S, Harris G, Tsipouras A, Wilson K, Kurtz M B.
Discovery of novel antifungal (1,3)-β-D-glucan synthase inhibitors.
Antimicrobial Agents & Chemotherapy.
2000;
44
368-77
-
7 Tkacz J S. Glucan biosynthesis in fungi and its Inhibition. In: Sutcliffe J, Georgopapadakou NH, editors Emerging Targets in Antibacterial and Antifungal Chemotherapy. New York; Chapman & Hall 1992: 495-523
-
8
Zacchino S A, Santecchia C B, López S N, Gattuso S J, Muñoz J D, Cruañes M C, Vivot E, Cruañes M J, Salinas A, Ruiz R, Ruiz S.
In vitro antifungal evaluation and studies on mode of action of eight selected species from the Argentine flora.
Phytomedicine.
1998;
5
389-95
-
9
Urbina J M, G-Cortés J C, Palma A, López S N, Zacchino S A, Enriz R D, Ribas J C, Kouznetsov V V.
Inhibitors of the fungal cell wall. Synthesis of 4-aryl-4-N-arylamine-1-butenes and related compounds with inhibitory activities on β(1 - 3)glucan and chitin synthases.
Bioorganic & Medicinal Chemistry.
2000;
8
691-8
-
10
López S N, Castelli M V, Zacchino S A, Domínguez J N, Lobo G, Charris Charris J, G-Cortés J C, Ribas J C, Devia C, Rodríguez A M, Enriz R D.
In vitro antifungal evaluation and structure-activity relationships of a new series of chalcone derivatives and synthetic analogues with inhibitory properties against the polymers of the fungal cell wall.
Bioorganic and Medicinal Chemistry.
2001;
9
1999-2013
-
11
Bah M, Pereda-Miranda R.
Detailed FAB-mass spectrometry and high resolution NMR investigations of tricolorins A-E, individual oligosaccharides from the resins of Ipomoea tricolor (Convolvulaceae).
Tetrahedron.
1996;
52
13 063-80
-
12
Bah M, Pereda-Miranda R.
Isolation and structural characterization of new glycolipid ester type dimers from the resin of Ipomoea tricolor (Convolvulaceae).
Tetrahedron.
1997;
53
9007-22
-
13
Hernández-Carlos B, Bye R, Pereda-Miranda R.
Orizabins V-VIII, tetrasaccharide glycolipids from the Mexican scammony root (Ipomoea orizabensis)
.
Journal of Natural Products.
1999;
62
1096-100
-
14
Pereda- Miranda R, Hernández-Carlos B.
HPLC isolation and structural elucidation of diastereomeric niloyl ester tetrasaccharides from Mexican scammony root.
Tetrahedron.
2002;
58
10 251-60
-
15
Varona R, Perez P, Durán A.
Effect of papulacandin B on β-glucan synthesis in Schizosaccharomyces pombe
.
FEMS Microbiology Letters.
1983;
20
243-7
-
16
Traxler P, Gruner J, Auden J.
Papulacandins, a new family of antibiotics with antifungal activity. I. Fermentation, isolation, chemical and biological characterization of papulacandins A, B, C, D and E.
Journal of Antibiotics.
1977;
30
289-96
-
17
Frost D J, Brandt K D, Capobianco J, Goldman R.
Characterization of 1,3-β-glucan synthase in Candida albicans: microsomal assay from the yeast or mycelial morphological forms and a permeabilized whole-cell assay.
Microbiology.
1994;
140
2239-46
-
18 Alfa C, Fantes P, Hyams J, McLeod M, Warbrick E. In: Alfa C, Fantes P, Hyams J, McLeod M, Warbrick, E, editors Experiments with fission yeast: a laboratory course manual. New York; Cold Spring Harbor Laboratory Press 1993: pp. 186
-
19
Ishiguro J, Saitou A, Durán A, Ribas J C.
Cps1+, a Schizosaccharomyces pombe gene homolog of Saccharomyces cerevisiae FKS genes whose mutation confers hypersensitivity to cyclosporin A and papulacandin B.
Journal of Bacteriology.
1997;
179
7653-62
Prof. Dra Susana A. Zacchino
Farmacognosia, Facultad Ciencias Bioquímicas y Farmacéuticas
Universidad Nacional de Rosario
Suipacha 531(2000)-Rosario
Argentina
Fax: +54-341-4375315
Email: szaabgil@citynet.net.ar