Indocarbazostatin and indocarbazostatin B, novel inhibitors of NGF-induced Neuronal differentiation in PC12 cells. II. Isolation, physicochemical properties and structural elucidation.
Two novel indolocarbazol-type bioactive molecules, indocarbazostatin (1) and indocarbazostatin B (2), were isolated as inhibitors of NGF-induced neuronal differentiation in rat pheochromocytoma PC12 cells from a culture broth of a Streptomyces sp. The structures of these compounds were determined by HR-FAB-MS, UV, 1H and 13C NMR, 1H-1H COSY, PFG HMBC, PFG HMQC and DIF NOE experiments. The relative and absolute configurations were deduced from MM2, MOPAC and CONFLEX calculations, and CD analyses. The imide/amide sector rule was proposed from the analyses of CD data of 1 and other indolocarbazole antibiotics. It was concluded that the minor compound 2 has a negative atropisomeric chirality in the aglycone.
Tamehiro
Norimasa
N
Biotechnology Research Center, Toyama Prefectural University, Kosugi, Japan.
Matsuura
Nobuyasu
N
Feng
Yufei
Y
Nakajima
Noriyuki
N
Ubukata
Makoto
M
D000818:Animals; D002227:Carbazoles / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002942:Circular Dichroism; D006131:Growth Inhibitors / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D007211:Indoles / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D013302:Streptomyces / Q000254:growth & development / Q000378:metabolism*
D002227:Carbazoles; D006131:Growth Inhibitors; D007211:Indoles; C402701:indocarbazostatin; C458887:indocarbazostatin B; D020932:Nerve Growth Factor