Anti-cancer polyketide compounds
Provided herein, inter alia, are anticancer polyketides. The uses of the polyketides described herein include treatment of cancer, for example, through regulation of the spliceosome and detection of spliceosome inhibition.
1. A compound having the formula:
wherein,
X 1 is N, O, or CH 2 ;
X 2 is O or C(R 6 )(R 7 ); and when X 2 is O then:
(i) the chiral carbon at R 2 has (R) stereochemistry and the chiral carbon at R 4 has (S) stereochemistry, and the compound is optically pure; or
(ii) the chiral carbon at R 2 has (S) stereochemistry and the chiral carbon at R 4 has (R) stereochemistry, and the compound is optically pure;
R 6 and R 7 are independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, —OR 12 , —OC(O)R 12 , —OC(O)OR 12 , or —OC(O)NR 13 R 14 ;
R 1 is —C(O)R 8 ;
R 2 is hydrogen or unsubstituted alkyl;
R 4 is —OR 9 ;
R 8 and R 9 are independently hydrogen or unsubstituted alkyl;
R 12 , R 13 and R 14 are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and
R 15 is hydrogen or unsubstituted alkyl.
2. The compound of claim 1 , having the formula:
3. The compound of claim 1 , wherein R 15 is hydrogen or C 1 -C 4 unsubstituted alkyl.
4. The compound of claim 3 wherein R 15 is methyl.
5. The compound of claim 2 wherein R 9 is hydrogen.
6. The compound of claim 4 , wherein X 2 is O.
7. The compound of claim 1 , wherein X 2 is C(R 6 )(R 7 ).
8. The compound of claim 7 , wherein R 6 and R 7 are independently hydrogen, halogen, or methyl.
9. The compound of claim 8 , wherein R 6 and R 7 are hydrogen or —F.
10. The compound of claim 1 having the formula:
11. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutical excipient.
12. A method of abating cancer, the method comprising administering to a subject in need thereof a therapeutically effective amount the compound of claim 1 .
13. The method of claim 12 , wherein the cancer is leukemia, lymphoma, metastatic cancer, or bone cancer.
14. The compound of claim 1 , wherein when X 2 is oxygen then the chiral carbon at R 2 has (R) stereochemistry and the chiral carbon at R 4 has (S) stereochemistry, and the compound is optically pure.