Zampanolides B-E from the Marine Sponge Cacospongia mycofijiensis: Potent Cytotoxic Macrolides with Microtubule-Stabilizing Activity.

Four new compounds (2-5) structurally related to the microtubule-stabilizing agent (-)-zampanolide (1) have been isolated from the Tongan marine sponge Cacospongia mycofijiensis. Three of these new structures, zampanolides B-D (2-4), exhibit nanomolar cytotoxicity toward the HL-60 cell line, are antimitotic, and induce in vitro tubulin polymerization at levels comparable to 1. Zampanolide E (5), saturated at C-8/C-9, was significantly less potent and does not stabilize purified tubulin, even at 10-fold higher concentrations.