Design, synthesis and functional characterization of rottlerin analogs
A method of synthesizing rottlerin analogs is described. The synthesis methods described are the first known method of synthesizing rottlerin analogs from commercially-available materials to produce cost effective analogs. Rottlerin analog structures made by the synthesis methods and methods of use for treating a neurological or inflammatory response mediated by protein kinase C (PKC) are further described.
1. A rottlerin analog comprising the following formula:
wherein R1 is selected from the group consisting of Ph (phenyl), phenol, CH 2 Ph, CH 2 -heterocycle and a substituted phenyl and wherein R2 is selected from the group consisting of halogens, H, OH, and benzyl, wherein said analog has biological PKCδ inhibitory potency exceeding natural rottlerin.
2. The analog of claim 1 wherein R1 is phenyl or R2 is a halogen.
3. The analog of claim 1 wherein R1 is a dihydroxy phenyl and R2 is a H.
4. The analog of claim 1 wherein R1 is a halo-phenyl and R2 is a H.
5. The analog of claim 1 wherein the phenol groups are replaced with methoxy groups.
6. A method of treating a neurological or inflammatory response mediated by protein kinase C (PKC) in an animal comprising:
administering to an animal in need thereof, an effective amount of a rottlerin analog according to claim 1 .
7. The method of claim 6 wherein said neurological or inflammatory response is Parkinson's disease.
8. A method for treating Parkinson's disease comprising:
modulating the activity of protein kinase C δ (PKCδ) by administering a rottlerin analog according to claim 1 .
9. A pharmaceutical composition for treating a neurological or inflammatory response mediated by protein kinase C (PKC) in an animal comprising:
a rottlerin analog according to claim 1 and a pharmaceutically acceptable carrier.