Synthesis of tetrocarcin derivatives with specific inhibitory activity towards Bcl-2 functions.
Tetrocarcin A was recently identified as an inhibitor of the anti-apoptotic function of Bcl-2. We synthesized novel tetrocarcin derivatives in order to increase their selective inhibitory activity against Bcl-2. It was found that 21-acetoxy-9-glycosyloxy derivatives had potent Bcl-2 inhibitory activity without significant antimicrobial activity.
Kaneko
M
M
Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd, Machida, Tokyo, Japan. masami.kaneko@kyowa.co.jp
Nakashima
T
T
Uosaki
Y
Y
Hara
M
M
Ikeda
S
S
Kanda
Y
Y
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000187:drug effects*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D013329:Structure-Activity Relationship
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D019253:Proto-Oncogene Proteins c-bcl-2; C025518:tetrocarcin A; D020169:Caspases