Eusynstyelamides A, B, and C, nNOS inhibitors, from the ascidian Eusynstyela latericius.
Eusynstyelamides A-C (1-3) were isolated from the Great Barrier Reef ascidian Eusynstyela latericius, together with the known metabolites homarine and trigonelline. The structures of 1-3, with relative configurations, were elucidated by interpretation of their spectroscopic data (NMR, MS, UV, IR, and CD). The NMR data of 1 were found to be virtually identical to that reported for eusynstyelamide (4), isolated from E. misakiensis, indicating that a revision of the structure of 4 is needed. Eusynstyelamides A-C exhibited inhibitory activity against neuronal nitric oxide synthase (nNOS), with IC(50) values of 41.7, 4.3, and 5.8 microM, respectively, whereas they were found to be nontoxic toward the three human tumor cell lines MCF-7 (breast), SF-268 (CNS), and H-460 (lung). Compounds 1 and 2 displayed mild inhibitory activity toward Staphylococcus aureus (IC(50) 5.6 and 6.5 mM, respectively) and mild inhibitory activity toward the C(4) plant regulatory enzyme pyruvate phosphate dikinase (PPDK) (IC(50) values of 19 and 20 mM, respectively).
Tapiolas
Dianne M
DM
Australian Institute of Marine Science, PMB no. 3, Townsville MC, Queensland, 4810, Australia. d.tapiolas@aims.gov.au
Bowden
Bruce F
BF
Abou-Mansour
Eliane
E
Willis
Richard H
RH
Doyle
Jason R
JR
Muirhead
Andrew N
AN
Liptrot
Catherine
C
Llewellyn
Lyndon E
LE
Wolff
Carsten W W
CW
Wright
Anthony D
AD
Motti
Cherie A
CA
D000818:Animals; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011772:Pyruvate, Orthophosphate Dikinase / Q000037:antagonists & inhibitors; D013211:Staphylococcus aureus / Q000187:drug effects; D014561:Urochordata / Q000737:chemistry*
D007211:Indoles; C542025:eusynstyelamide A; C542026:eusynstyelamide B; C542027:eusynstyelamide C; D052248:Nitric Oxide Synthase Type I; D011772:Pyruvate, Orthophosphate Dikinase