TAN-999 and TAN-1030A, new indolocarbazole alkaloids with macrophage-activating properties

Two new indolocarbazole alkaloids, TAN-999 and TAN-1030A, were isolated from culture broths of Nocardiopsis dassonvillei C-71425 and Streptomyces sp. C-71799, respectively. Their structures were elucidated on the basis of their reactions, spectroscopic analyses and in particular, comparison of spectral data with that of staurosporine. These metabolites induced spreading of a murine macrophage cell line, Mm 1. They also augmented the phagocytic activity, Fc gamma receptor expression and beta-glucuronidase activity of murine macrophage cell lines, Mm 1 and J774A.1. When proteose-peptone elicited peritoneal macrophages from mice were incubated with these metabolites for 2 days, the phagocytosis-dependent respiratory burst of these cells was enhanced. Similar enhancement was also observed when the peritoneal macrophages in mice were modulated by intraperitoneal administration of these metabolites. These results reveal that TAN-999 and TAN-1030A can activate macrophage functions in mice.