Isolation, identification, and uses of antifungal compounds

Patent metadata

Field	Value
Publication number	US-9879048-B2
Application number	US-201214367277-A
Country	US
Kind code	B2
Filing date	Dec 20, 2012
Priority date	Dec 20, 2010
Publication date	Jan 30, 2018
Grant date	Jan 30, 2018

Abstract

In one aspect, the invention relates to isolated compounds useful as antifungal agents, for example, compounds having a structure represented by a formula: wherein R 1 is hydrogen or hydroxyl; wherein R 2 is hydrogen, a-xylose or β-xylose; and wherein R 3 and R 4 are each hydrogen or together oxygen, or a pharmaceutically acceptable salt thereof; methods of isolating and purifying same; pharmaceutical compositions comprising same; agricultural compositions comprising same; and methods of treating and/or preventing fungal infections using same. In one aspect, R 2 is not hydrogen or β-xylose when R 1 is hydroxyl and R 3 and R 4 are together oxygen. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

First claim

The invention claimed is:

1. A pharmaceutical composition comprising a compound having a structure represented by a formula:

wherein R 1 is hydrogen or hydroxyl;
wherein R 2 is α-xylose or β-xylose; and
wherein R 3 and R 4 are each hydrogen;
or a pharmaceutically acceptable salt thereof, and
a pharmaceutically acceptable carrier selected from aerosol, cream, ointment, lotion, dusting powder, liposome, microcapsule, emulsion, and polymeric encapsulation or combination thereof.

2. The composition of claim 1 , wherein R 1 is hydrogen.

3. The composition of claim 1 , wherein R 1 is hydroxyl.

4. The composition of claim 1 , wherein R 2 has a structure represented by a formula:

5. The composition of claim 1 , wherein R 2 has a structure represented by a formula:

6. The composition of claim 1 , wherein R 1 is hydroxyl; R 2 is α-xylose; and R 3 and R 4 are each hydrogen.

7. The composition of claim 1 , wherein R 1 is hydrogen; R 2 is β-xylose; and R 3 and R 4 are each hydrogen.

8. The composition of claim 1 , wherein the compound is cytotoxic.

9. The composition of claim 1 , wherein the compound exhibits antifungal activity against Alternaria, Aspergillus, Botrytis, Cercospora, Cercosporidium, Erysiphe, Geotrichum, Mycosphaerella, Mucor, Penicillium, Phoma, Phytophthora, Plasmopora, Pseudopeziza, Puccinia, Pythium, Rhizoctonia, Rhizopus, Septoria, Sporothrix, Stemphylium, Trichophyton , or Verticillium.

10. The composition of claim 1 , wherein the compound is isolated from a culture of Burkholderia ambifaria.

11. A method for the treatment of an animal having a fungal infection, comprising administering to the animal a pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound, or a pharmaceutically acceptable salt thereof, having a structure represented by a formula:

wherein R 1 is hydrogen or hydroxyl;
wherein R 2 is α-xylose or β-xylose; and
wherein R 3 and R 4 are each hydrogen,
thereby treating the fungal infection in the animal,
wherein the fungal infection is selected from infections of Botrytis sp., Mycosphaerella sp., Cercospora sp., Rhizoctonia sp., Sclerotinia sp., Pythium sp., Phytophthora sp., Alternaria sp., Saccharamyces sp., Candida sp., Aspergillus sp., Pseudocercosporella sp., Cladosporium sp., Penicillium sp., Chaetomium sp., Fusarium sp., Pyricularia sp., Erysiphe sp., Spaerotheca sp., Leptosphaeria sp, Plasmopara sp., and Colletotrichum sp.

12. The method of claim 11 , wherein the fungal infection is cutaneous.

13. A method for the treatment of a plant having a fungal infection, comprising administering to the plant an agricultural composition comprising a agriculturally acceptable carrier and an effective amount of a compound, or a pharmaceutically acceptable salt thereof, having a structure represented by a formula:

wherein R 1 is hydrogen or hydroxyl;
wherein R 1 is hydrogen or hydroxyl;
wherein R 2 is α-xylose or β-xylose; and
wherein R 3 and R 4 are each hydrogen,
thereby treating the fungal infection in the plant,
wherein the fungal infection is selected from infections of Botrytis sp., Mycosphaerella sp., Cercospora sp., Rhizoctonia sp., Sclerotinia sp., Pythium sp., Phytophthora sp., Alternaria sp., Saccharamyces sp., Candida sp., Aspergillus sp., Pseudocercosporella sp., Cladosporium sp., Penicillium sp., Chaetomium sp., Fusarium sp., Pyricularia sp., Erysiphe sp., Spaerotheca sp., Leptosphaeria sp, Plasmopara sp., and Colletotrichum sp.

14. The method of claim 13 , wherein the application is foliar.

15. A pharmaceutical composition comprising a pharmaceutically acceptable salt of a compound having a structure represented by a formula:

wherein R 1 is hydrogen or hydroxyl;
wherein R 2 is α-xylose or β-xylose; and
wherein R 3 and R 4 are each hydrogen, and
a pharmaceutically acceptable carrier.

16. The composition of claim 15 , wherein R 1 is hydrogen.

17. The composition of claim 15 , wherein R 1 is hydroxyl.

18. The composition of claim 15 , wherein R 2 has a structure represented by a formula:

19. The composition of claim 15 , wherein R 2 has a structure represented by a formula:

20. The composition of claim 15 , wherein R 1 is hydroxyl; R 2 is α-xylose; and R 3 and R 4 are each hydrogen.

21. The composition of claim 15 , wherein R 1 is hydrogen; R 2 is β-xylose; and R 3 and R 4 are each hydrogen.

22. The composition of claim 15 , wherein the compound is cytotoxic.

23. The composition of claim 15 , wherein the compound exhibits antifungal activity against Alternaria, Aspergillus, Botrytis, Cercospora, Cercosporidium, Erysiphe, Geotrichum, Mycosphaerella, Mucor, Penicillium, Phoma, Phytophthora, Plasmopora, Pseudopeziza, Puccinia, Pythium, Rhizoctonia, Rhizopus, Septoria, Sporothrix, Stemphylium, Trichophyton , or Verticillium.

24. The composition of claim 15 , wherein the compound is isolated from a culture of Burkholderia ambifaria.

25. The composition of claim 15 , wherein the pharmaceutically acceptable carrier is selected from aerosol, cream, ointment, lotion, dusting powder, liposome, microcapsule, emulsion, and polymeric encapsulation or combination thereof.

Assignees

• Univ Utah Res Found
• Virginia Tech Intellectual Properties Inc

Inventors

• Schmidt Eric W
• Falkinham Joseph O
• Jeffs Peter W

Classifications

• C07K9/006

  the peptide sequence being part of a ring structure · CPC title

• A61K38/14

  Peptides containing saccharide radicals; Derivatives thereof {, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin} · CPC title

• C07K7/56 Primary

  the cyclisation not occurring through 2,4-diamino-butanoic acid · CPC title

• A61K38/12

  Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)} · CPC title

• C07K9/00

  Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof · CPC title