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

Taufa, Taitusi and Singh, A. Jonathan and Harland, Chloe R. and Patel, Vimal and Jones, Ben and Halafihi, Tu′ikolongahau and Miller, John H. and Keyzers, R. A. and Northcote, P. T. (2018) Zampanolides B−E from the Marine Sponge Cacospongia mycofijiensis: Potent Cytotoxic Macrolides with Microtubule- Stabilizing Activity. Journal of Natural Products, 81 (11). pp. 2539-2544. ISSN 0163-3864

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Abstract

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. The structural differences across these
compounds reveal a plasticity of the zampanolide pharmacophore.
While unsaturation is required at Δ8, the configuration
of this alkene and those of Δ4 and Δ4′ have little effect on
tubulin polymerization. The first natural co-occurrence of 1 and (−)-dactylolide (6) from the same sponge extract is also noted

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry
Divisions:	Faculty of Science, Technology and Environment (FSTE) > School of Biological and Chemical Sciences
Depositing User:	Taitusi Taufa
Date Deposited:	19 Jun 2019 00:22
Last Modified:	19 Jun 2019 00:22
URI:	https://repository.usp.ac.fj/id/eprint/11604

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