6533b829fe1ef96bd12899f4

RESEARCH PRODUCT

Cytotoxic and protein kinase inhibiting nakijiquinones and nakijiquinols from the sponge Dactylospongia metachromia.

Victor WrayWerner E.g. MüllerWenhan LinAmal H. AlyPeter ProkschMichael H.g. KubbutatGeorgios DaletosNicole J. De VoogdDaniel Feger

subject

Pharmaceutical ScienceAntineoplastic AgentsMarine BiologySesquiterpeneAnalytical Chemistrychemistry.chemical_compoundInhibitory Concentration 50MiceDrug DiscoveryAnimalsHumansProtein kinase ACytotoxicityIC50Nuclear Magnetic Resonance BiomolecularProtein Kinase InhibitorsPharmacologyBenzoxazolesMolecular StructureKinaseOrganic ChemistryQuinonesIn vitroPoriferaComplementary and alternative medicineBiochemistrychemistryCell cultureMolecular MedicineDrug Screening Assays AntitumorSesquiterpenesProto-oncogene tyrosine-protein kinase Src

description

Chemical investigation of the sponge Dactylospongia metachromia afforded five new sesquiterpene aminoquinones (1-5), two new sesquiterpene benzoxazoles (6 and 7), the known analogue 18-hydroxy-5-epi-hyrtiophenol (8), and a known glycerolipid. The structures of all compounds were unambiguously elucidated by one- and two-dimensional NMR and by MS analyses, as well as by comparison with the literature. Compounds 1-5 showed potent cytotoxicity against the mouse lymphoma cell line L5178Y with IC50 values ranging from 1.1 to 3.7 μM. When tested in vitro for their inhibitory potential against 16 different protein kinases, compounds 5, 6, and 8 exhibited the strongest inhibitory activity against ALK, FAK, IGF1-R, SRC, VEGF-R2, Aurora-B, MET wt, and NEK6 kinases (IC50 0.97-8.62 μM).

yearjournalcountryeditionlanguage
2014-02-01Journal of natural products
10.1021/np400633mhttps://pubmed.ncbi.nlm.nih.gov/24479418