Antifungals targeted to sphingolipid synthesis: Focus on inositol phosphorylceramide synthase

Expert Opinion on Investigational Drugs

Volumn 9, Issue 8, 2000, Pages 1787-1796

  Georgopapadakou, N H ^a  

^a DUPONT COMPANY   (United States)

Author keywords

Antifungals; Aureobasidins; Fungal sphingolipids; Inositol phosphorylceramide synthase

Indexed keywords

ANIDULAFUNGIN; ANTIFUNGAL AGENT; AUREOBASIDIN A; AUSTRALIFUNGIN; CASPOFUNGIN; CERAMIDE; CYCLOSERINE; ENZYME INHIBITOR; ERGOSTEROL; FUMONISIN B1; GALBONOLIDE A; GLUCAN SYNTHASE; INOSITOL PHOSPHORYLCERAMIDE SYNTHASE; ISP 1; KHAFREFUNGIN; LIPOXAMYCIN; MICAFUNGIN; MYRIOXIN; NATURAL PRODUCT; PALMITOYL COENZYME A; POLYENE; PYRROLE DERIVATIVE; RUSTIMYCIN; SPHINGOFUNGIN C; SPHINGOLIPID; SPHINGOSINE ACYLTRANSFERASE; SYNTHETASE; TRIAZOLE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VIRIDIOFUNGIN;

ANTIFUNGAL ACTIVITY; BIOSYNTHESIS; CELL MEMBRANE; CLINICAL MEDICINE; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DRUG RESISTANCE; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG TARGETING; ENZYME INHIBITION; EUKARYOTIC CELL; FUNGUS; HUMAN; LIPOGENESIS; MAMMAL CELL; MYCOSIS; REVIEW;

EID: 0033895268     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.9.8.1787     Document Type: Review

References (61)

1. Invasive fungal infections: Problems and challenges for developing new antifungal compounds
2. Secular trends in the epidemiology of nosocomial fungal infections in the United States, 1980-1990. National Nosocomial Infections Surveillance System
3. Human mycoses: Drugs and targets for emerging pathogens
4. Antifungal agents: Chemotherapeutic targets and immunologic strategies
5. Antifungals: Mechanism of action and resistance, established and novel drugs
6. Antifungals targeted to the cell wall
7. Current and emerging azole antifungal agents
8. Multiple resistance mechanisms to azole antifungals in yeast clinical isolates
9. Clinical, cellular and molecular factors that contribute to antifungal drug resistance
10. Glucan biosynthesis as a target for antifungals: The echinocandin class of antifungal agents
11. Lipopeptide inhibitors of fungal glucan synthase
12. Sphingolipid functions in Saccharomyces cerevisiae: Comparison to mammals
13. Sphingolipids with inositolphosphate-containing head groups
14. Yeast sphingolipids
15. Suppressor gene analysis reveals an essential role for sphingolipids in transport of glycosylphosphatidylinositol-anchored proteins in Saccharomyces cerevisiae
16. Characterization of sphingolipids from mycopathogens: Specific factors correlating with expression of 2-hydroxy fatty acyl (E)-Delta 3-unsaturation in cerebrosides of Paracoccidioides brasiliensis and Aspergillus fumigatus
17. Inhibition of inositol phosphorylceramide synthase by aureobasidin A in Candida and Aspergillus species
18. Sphingolipids: Metabolism and cell signaling
19. Structure and function of sphingolipid- and cholesterol-rich membrane rafts
20. Physiology and pathophysiology of sphingolipid metabolism and signaling
21. Ceramide: A novel second messenger and lipid mediator
22. Ceramide in the eukaryotic stress response
23. Structure of aureobasidin A
24. Sphingolipid synthesis as a target for antifungal drugs. Complementation of the inositol phosphorylceramide synthase defect in a mutant of Saccharomyces cerevisiae by the AUR1 gene
25. Fungicidal action of aureobasidin A, a cyclic depsipeptide antifungal antibiotic, against Saccharomyces cerevisiae
26. Cloning and characterization of LCB1, a Saccharomyces gene required for biosynthesis of the long-chain base component of sphingolipids
27. The LCB2 gene of Saccharomyces and the related LCB1 gene encode subunits of serine palmitoyltransferase, the initial enzyme in sphingolipid synthesis
28. 2+-sensitive yeast mutant (csg2) identify genes involved in sphingolipid biosynthesis. Cloning and characterization of SCS1, a gene required for serine palmitoyltransferase activity
29. Tsc3p is an 80-amino acid protein associated with serine palmitoyltransferase and required for optimal activity
30. 2+-sensitive Δcsg2 mutant
31. Syringomycin gene SYR2 is essential for sphingolipid 4-hydroxylation in Saccharomyces cerevisiae
32. ELO2 and ELO3, homologues of the Saccharomyces cerevisiae ELO1 gene, function in fatty acid elongation and are required for sphingolipid formation
33. The AUR1 gene in Saccharomyces cerevisiae encodes dominant resistance to the antifungal agent Aureobasidin A (LY295337)
34. AUR1, a novel gene conferring aureobasidin resistance on Saccharomyces cerevisiae: A study of defective morphologies in Aur1p-depleted cells
35. Inhibition of yeast inositol phosphorylceramide synthase by aureobasidin A measured by a fluorometric assay
36. 2+ concentrations at 37°C, is required for mannosylation of inositolphosphorylceramide
37. Synthesis of mannose(inositol-P) 2-ceramide, the major sphingolipid in Saccharomyces cerevisiae, requires the IPT1 (YDR072c) gene
38. The yeast mic2 mutant is defective in the formation of mannosyl-diinositolphosphoryl ceramide
39. Fumonisins and other inhibitors of de novo sphingolipid biosynthesis
40. Characterization of a novel, potent and specific inhibitor of serine palmitoyltransferase
41. Sphingofungins E and F: Novel serine palmitoyltransferase inhibitors from Paecilomyces variotii
42. Inhibition of serine palmitoyltransferase activity by lipoxamycin
43. Serine palmitoyltransferase is the primary target of a sphingosine-like immunosuppressant, ISP-1/myriocin
44. Viridiofungins, novel inhibitors of sphingolipid synthesis
45. Inhibition of sphingolipid biosynthesis by fumonisins. Implications for diseases associated with Fusarium moniliforme
46. Fumonisins and other inhibitors of de novo sphingolipid biosynthesis
47. The discovery of australifungin, a novel inhibitor of sphinganine N-acyltransferase from Sporormiella australis. Producing organism, fermentation, isolation and biological activity
48. Structure of aureobasidin A
49. Aureobasidins, new antifungal antibiotics: Taxonomy, fermentation, isolation and properties
50. Biological properties of aureobasidin A, a cyclic depsipeptide antifungal antibiotic
51. Role of ABC transporters in aureobasidin A resistance
52. Structures and antifungal activities of new aureobasidins
53. Khafrefungin, a novel inhibitor of sphingolipid synthesis
54. The galbonolides. Novel powerful antifungal macrolides from Streptomyces galbus spp Eurythermus
55. Rustmicin, a potent antifungal agent, inhibits sphingolipid synthesis at inositol phosphoceramide synthase
56. Inhibition of fungal sphingolipid biosynthesis by rustmicin, galbonolide B and their new 21-hydroxy analogs
57. LY295337 a novel cyclic depsipeptide antifungal antibiotic. I. In vitro antifungal activity
58. LY295337 a novel cyclic depsipeptide antifungal antibiotic. II. In vivo antifungal activity
59. LY295337 a novel cyclic depsipeptide antifungal antibiotic. III. Resistance development studies
60. A novel antifungal cyclodepsipeptide: Synthesis and structure-activity relationships of new cyclodepsipeptides
61. Total synthesis of the antifungal cyclic depsipeptides SCH 53174 and 54256