Spirastrellolide A, an antimitotic macrolide isolated from the Caribbean marine sponge Spirastrella coccinea.
Sprirastrellolide A, a novel antimitotic macrolide, has been isolated from the Caribbean marine sponge Spirastrella coccinea. It has a 47-carbon linear polyketide backbone incorporated into a highly functionalized 38-membered lactone containing a tetrahydropyran and two spiro bispyran substructures embedded in the macrocycle and a side chain terminating in a carboxylic acid. Sprirastrellolide A's structure was elucidated by detailed spectroscopic analysis of its methyl ester 2. Spirastrellolide A methyl ester 2 shows potent activity in a cell-based assay that detects mitotic arrest, but it does not affect tubulin polymerization in vitro. It has the unusual biological property of being able to accelerate the entry of cells into mitosis from other cell-cycle stages, before it arrests them in mitosis.
Williams
David E
DE
Department of Chemistry, University of British Columbia, Vancouver, BC, Canada V6T 1Z1.
Roberge
Michel
M
Van Soest
Rob
R
Andersen
Raymond J
RJ
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification; D018942:Macrolides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011161:Porifera / Q000737:chemistry*; D013141:Spiro Compounds
D000970:Antineoplastic Agents; D018942:Macrolides; D013141:Spiro Compounds; C475125:spirastrellolide A