Gracilin A and congeners as immunosuppressive and neuroprotective agents

1. A method for suppressing an immune response in a subject, the method comprising administering to a subject in need thereof an effective amount of a compound having the formula:

or a stereoisomer or racemate thereof, wherein:

R 1 , R 2 , and R 3 are independently H or C1-C3 alkyl, and the dashed line denotes a bond or an absence of a bond, with the proviso that only one dashed line is a bond.

2. The method of claim 1 , wherein the compound is:

or a stereoisomer or racemate thereof.

3. The method of claim 1 , wherein the compound is:

4. The method of claim 1 , wherein the subject has been diagnosed as suffering from an autoimmune disease or an inflammatory disease.

5. The method of claim 1 , wherein the compound inhibits interleukin-2 production.

6. The method of claim 5 , wherein the interleukin-2 production is inhibited by greater than about 20%.

7. The method of claim 1 , wherein the compound binds to CypA with a K D of less than about 6 μM.

8. The method of claim 1 , wherein the compound reduces T-cell viability in vitro by less than about 10%.

9. A method for treating a neurodegenerative disease in a subject, the method comprising administering to a subject in need thereof an effective amount of a compound having the formula:

or a stereoisomer or racemate thereof, wherein:

R 1 , R 2 , and R 3 are independently H or C1-C3 alkyl;

R 4 is H, OH, OAc, or absent;

R 5 and R 8 are independently H or OAc;

R 6 and R 7 are H or R 6 and R 7 , taken together, are O; and

the dashed line denotes a bond when R 4 is absent, or absence of a bond when R 4 is H, OH, or OAc.

10. The method of claim 9 , wherein the compound is:

or a stereoisomer or racemate thereof.

11. The method of claim 9 , wherein the compound is:

12. The method of claim 9 , wherein the neurodegenerative disease is Alzheimer's disease.

13. The method of claim 9 , wherein the compound inhibits CypD with an IC 50 of less than about 0.5 μM.

14. The method of claim 9 , wherein the compound inhibits CypA with an IC 50 of less than about 0.3 μM.

15. The method of claim 9 , wherein the compound inhibits CypD and does not inhibit CypA.

16. A compound having the formula:

or a stereoisomer or racemate thereof, wherein:

R 1 , R 2 , and R 3 are independently H or C1-C3 alkyl;

R 4 is H, OH, OAc, or absent;

R 5 and R 8 are independently H or OAc;

R 6 and R 7 , taken together, are O; and

the dashed line denotes a bond or absence of a bond with the proviso that only one dashed line is a bond, and with a further proviso that both dashed lines denote absence of a bond when R 4 is H, OH, or OAc.

17. The compound of claim 16 , wherein the compound is:

or a stereoisomer or racemate thereof.

18. The compound of claim 16 selected from the group consisting of:

19. A pharmaceutical composition, comprising a compound of claim 16 and a pharmaceutically acceptable carrier.

20. A method for suppressing an immune response in a subject, the method comprising administering to a subject in need thereof an effective amount of a compound having the formula:

21. A compound having the formula:

22. A pharmaceutical composition, comprising a compound of claim 21 and a pharmaceutically acceptable carrier.