Stereoselective synthesis and osteogenic activity of subglutinols A and B.
Since clinically approved immunosuppressive drugs (e.g., cyclosporin A, FK506) possess dose-dependent biphasic effects that cause undesirable side effects on bone structure, including osteopenia, osteoporosis, and increased incidence of bone fractures, considerable effort has been devoted to the identification of immunosuppressive drugs that promote bone formation in a dose-dependent manner. Herein, we report the stereoselective synthesis of subglutinols A and B and present initial biological data showing the significant potential of subglutinol A as an immunosuppressive drug with dose-dependent osteogenic activity. We also show that activating protein 1 (AP-1) family transcription factors could be one of the key regulators for the anabolic activity of subglutinol A. Such drugs with dose-dependent osteogenic activity might help reduce bone-associated side effects and be clinically useful for bone tissue transplantation.
Kim
Hyoungsu
H
Department of Chemistry, Duke University, Durham, North Carolina 27708, USA.
Baker
Joseph B
JB
Lee
Su-Ui
SU
Park
Yongho
Y
Bolduc
Kyle L
KL
Park
Hyung-Bae
HB
Dickens
Marina G
MG
Lee
Dong-Sup
DS
Kim
Yongchul
Y
Kim
Seong Hwan
SH
Hong
Jiyong
J
D000818:Animals; D002460:Cell Line; D018360:Crystallography, X-Ray; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005670:Fusarium / Q000737:chemistry*; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D010012:Osteogenesis / Q000187:drug effects*; D011753:Pyrones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism
D004224:Diterpenes; D007166:Immunosuppressive Agents; D011753:Pyrones; C551806:subglutinol A; C551807:subglutinol B