title: Spiralisones A-D: acylphloroglucinol hemiketals from an Australian marine brown alga, Zonaria spiralis.
abstract: An intertidal sample of the Australian marine brown alga, Zonaria spiralis, exhibited promising kinase inhibitory and antibacterial activity. Chemical analysis returned six phloroglucinol-derived lipids, the new hemiketal spiralisones A-D (1-4) and the known chromones 5-6, and the known norsesquiterpenoid apo-9'-fucoxanthinone (7). Structures 1-7 were assigned on the basis of detailed spectroscopic analysis, biosynthetic considerations and total synthesis. Spiralisones undergo facile acid-mediated dehydration to yield the corresponding chromones, revealing for the first time that brown algal chromones may be handling artifacts rather than natural products. Hemiketals 1 and 2, and chromone 6, displayed inhibitory activity against the neurodegenerative disease kinase targets CDK5/p25, CK1δ and GSK3β, while hemiketals 1, 3 and 4, and chromone 6, displayed growth inhibitory activity against the Gram-positive bacteria Bacillus subtilis (ATCC 6051 and 6633). The promising kinase inhibitory and antibacterial properties of the Z. spiralis extract were attributed to the cumulative effect of many moderately potent phloroglucinol-derived lipid co-metabolites.
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland 4072, Australia.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Xue
authors.initials: X
authors.lastname: Xiao
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Conte
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Khalil
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Capon
mesh_terms: D000215:Acylation; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001315:Australia; D001412:Bacillus subtilis / Q000187:drug effects; D015394:Molecular Structure; D019636:Neurodegenerative Diseases / Q000201:enzymology; D019906:Nuclear Magnetic Resonance, Biomolecular; D000459:Phaeophyceae / Q000737:chemistry* / Q000254:growth & development; D010696:Phloroglucinol / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D047428:Protein Kinase Inhibitors; D010696:Phloroglucinol