Four new bioactive manzamine-type alkaloids from the Philippine marine sponge Xestospongia ashmorica.
Analysis of the Philippine marine sponge Xestospongia ashmorica afforded four new manzamine congeners 1-4 and four known compounds 5 and 7-9. Compound 1 is the 6-deoxy derivative of manzamine X, while 2-4 are the N-oxides of manzamine J (5), 3,4-dihydromanzamine A (6), and manzamine A (7), respectively. The structures of the new compounds were unambiguously established on the basis of NMR spectroscopic (1H, 13C, COSY, 1H-detected direct, and long-range 13C-1H correlations) and mass spectrometric (EI, FAB-MS, and electrospray ionization) data. Alkaloid N-oxide structures were confirmed by conversion to the corresponding tertiary bases by reduction with Zn/HCl. This is the first report of the occurrence of bioactive manzamine N-oxides in marine sponges. Compound 7 exhibited insecticidal activity toward neonate larvae of the polyphagous pest insect Spodoptera littoralis (with an ED50 of 35 ppm) when incorporated in artificial diet and offered to larvae in a chronic feeding bioassay. Compound 7 was also active against the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus. Cytotoxicity was studied in vitro using L1578y mouse lymphoma cells. From the alkaloids studied, the N-oxides 3 and 4 were the most active (ED50 = 1.6 micrograms/mL) followed by compound 7 (ED50 = 1.8 micrograms/mL).
Edrada
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RA
Julius-von-Sachs-Institut für Biowissenschaften, Lehrstuhl für Pharmazeutische Biologie, Würzburg, Germany.
Proksch
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P
Wray
V
V
Witte
L
L
Müller
W E
WE
Van Soest
R W
RW
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D007306:Insecticides / Q000302:isolation & purification / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008826:Microbial Sensitivity Tests; D010679:Philippines; D011161:Porifera / Q000737:chemistry*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013055:Spectrophotometry, Infrared; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D007306:Insecticides