Anti-inflammatory compounds
New clerodane compounds isolated from plant material from Dodonaea polyandra are disclosed. The compounds have anti-inflammatory activity. Pharmaceutical and cosmetic compositions containing the compounds, as well as methods of treating inflammation using the compounds, are also disclosed.
1. A compound of formula (I)
or a pharmaceutically acceptable salt or an ester prodrug thereof, wherein:
T is a double bond;
R 1 is selected from the group consisting of: COOR 7 , CONR 7 R 8 , COSR 7 , COR 7 , SO 3 H, SO 2 NR 7 R 8 , SO 2 R 7 , SONR 7 R 8 , and SOR 7 ;
R 2 , R 3 , and R 4 are each independently selected from the group consisting of: H, optionally substituted C1-C12 alkyl, and optionally substituted C2-C12 alkenyl;
R 5 and R 6 are each independently selected from the group consisting of: H, OH, optionally substituted C1-C12 alkyl, ═O, (CH 2 )mOC(O)R 9 , C1-C12 oxyalkyl, C1-C12 alkyloxy, C2-C12 oxyalkenyl, and C2-C12 alkenyloxy, provided at least one of R 5 and R 6 is (CH 2 )mOC(O)R 9 ;
R 7 and R 8 are each independently selected from the group consisting of: H, optionally substituted C1-C12 alkyl, optionally substituted C2-C12 alkenyl, optionally substituted C2-C12 alkynyl, optionally substituted C1-C10 heteroalkyl, optionally substituted C3-C12 cycloalkyl, optionally substituted C3-C12 cycloalkenyl, optionally substituted C1-C12 heterocycloalkyl, optionally substituted C1-C12 heterocycloalkenyl, optionally substituted C6-C18 aryl, and optionally substituted C1-C18 heteroaryl;
R 9 is phenyl;
Ar is an optionally substituted aryl group; and
m and n are integers each of which is selected from the group consisting of 0, 1, 2, 3, and 4.
2. The compound of claim 1 , wherein only one of R 5 and R 6 is (CH 2 )mOC(O)R 9 .
3. The compound of claim 1 , wherein Ar is selected from the group consisting of: optionally substituted furan, optionally substituted thiophene, optionally substituted pyrrole, optionally substituted phenyl, and optionally substituted pyridine.
4. The compound of claim 3 , wherein Ar is furan.
5. The compound of claim 1 , wherein R 1 is COOR 7 .
6. The compound of claim 1 , wherein R 2 is methyl.
7. The compound of claim 1 , wherein R 3 is H.
8. The compound of claim 1 , wherein R 4 is optionally substituted C1-C12 alkyl.
9. The compound of claim 8 , wherein R 4 is methyl.
10. The compound of claim 1 , wherein R 5 is (CH 2 )mOC(O)R 9 and R 6 is selected from the group consisting of H and OH.
11. The compound of claim 1 , wherein R 6 is (CH 2 )mOC(O)R 9 and R 5 is optionally substituted C1-C12 alkyl.
12. A compound selected from the group consisting of:
13. An anti-inflammatory Dodonaea polyandra extract comprising a compound of claim 1 .
14. The anti-inflammatory extract of claim 13 , wherein the extract comprises a benzoyl ester clerodane diterpenoid.
15. A composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.
16. A method of treating inflammation in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound according to claim 1 .
17. A method of treating inflammation, the method comprising administering to a subject in need of such treatment a therapeutically effective amount of an extract according to claim 13 .