Indocarbazostatin and Indocarbazostatin B, Novel Inhibitors of NGF-induced Neuronal Differentiation in PC12 Cells

II. Isolation, Physicochemical Properties and Structural Elucidation

Abstract

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.