Cytotoxic and protein kinase inhibiting nakijiquinones and nakijiquinols from the sponge Dactylospongia metachromia.
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).
Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität , Universitätsstraße 1, 40225 Düsseldorf, Germany.
Georgios
G
Daletos
Nicole J
NJ
de Voogd
Werner E G
WE
Müller
Victor
V
Wray
WenHan
W
Lin
Daniel
D
Feger
Michael
M
Kubbutat
Amal H
AH
Aly
Peter
P
Proksch
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001583:Benzoxazoles / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D008386:Marine Biology; D051379:Mice; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011161:Porifera / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D011809:Quinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
D000970:Antineoplastic Agents; D001583:Benzoxazoles; D047428:Protein Kinase Inhibitors; D011809:Quinones; D012717:Sesquiterpenes