11-Hydroxystaurosporine: a highly cytotoxic, powerful protein kinase C inhibitor from a tunicate

The Journal of Organic Chemistry
1992.0

Abstract

Ascidians, the largest class in the subphylum urochordata (tunicates), are highly developed sessile animals often rich in bioactive secondary metabolites. Noteworthy examples are the didemnins, depsipeptides that show considerable promise as antitumor agents, the antiviral β-carbolines such as the eudistomins, cytotoxic iminoquinone pigments like wakayin and the discorhabdins, and the pentacyclic alkaloid shermilamine. The indolo[2,3-a]carbazole ring system is not represented among alkaloids isolated from marine sources, although numerous indolocarbazoles are known from terrestrial microorganisms, slime molds, and more recently, from fresh water blue-green algae. We report here the isolation and structure proof of 11-hydroxystaurosporine (2), the first indolo[2,3-a]carbazole to be isolated from a marine organism. A dihydroxy derivative, 3,11-dihydroxystaurosporine (3), was also isolated but was incompletely characterized due to lack of material. Both are active against human nasopharyngeal cancer cells, and 2 is more potent than staurosporine (1) in protein kinase C (PKC) inhibition.

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