Chemical and biological investigation of the cultured marine hydrothermal vent bacterium, Thermovibrio ammonifican led to the isolation of two hydroxyethylamine chromene derivatives, ammonificins C and D. Their structures were elucidated using combination of NMR and mass spectrometry. Absolute stereochemistry was ascertained by comparison of experimental and calculated CD spectra. Biological evaluation and assessment were determined using the patented ApopScreen cell-based screen for apoptosis-induction. Ammonificins C and D induce apoptosis in micromolar concentrations. To our knowledge, this finding is the first report of chemical compounds that induce apoptosis from the cultured deep-sea marine organism, hydrothermal vent bacterium, Thermovibrio ammonificans.
References
[1]
G？rtner, A.; Wiese, J.; Imhoff, J.F. Amphritea atlantica gen. nov., sp. nov., a gammaproteobacterium from the Logatchev hydrothermal vent field. Int. J. Syst. Evol. Microbiol. 2008, 58, 34–39, doi:10.1099/ijs.0.65234-0.
[2]
Thornburg, C.C.; Zabriskie, T.M.; McPhail, K.L. Deep-sea hydrothermal vents: Potential hot spots for natural products discovery? J. Nat. Prod. 2010, 73, 489–499, doi:10.1021/np900662k.
[3]
Kicklighter, C.E.; Fisher, C.R.; Hay, M.E. Chemical defense of hydrothermal vent and hydrocarbon seep organisms: A preliminary assessment using shallow-water consumers. Mar. Ecol. Prog. Ser. 2004, 275, 11–19, doi:10.3354/meps275011.
[4]
Vetriani, C.; Speck, M.D.; Ellor, S.V.; Lutz, R.A.; Starovoytov, V. Thermovibrio ammonificans sp. nov., a thermophilic, chemolithotrophic, nitrate ammonifying bacterium from deep-sea hydrothermal vent. Int. J. Syst. Evol. Microbiol. 2004, 54, 175–181, doi:10.1099/ijs.0.02781-0.
[5]
Andrianasolo, E.H.; Haramaty, L.; Degenhardt, K.; Mathew, R.; White, E.; Lutz, R.; Falkowski, P. Induction of apoptosis by diterpenes from the soft coral Xenia elongata. J. Nat. Prod. 2007, 70, 1551–1557, doi:10.1021/np070088v.
[6]
Mathew, R.; Degenhart, K.; Haramaty, L.; Karp, C.M.; White, E. Immortalized mouse epithelial cell models to study the role of apoptosis in cancer. Methods Enzymol. 2008, 446, 77–106.
[7]
Karantza-Wadsworth, V.; White, E. Programmed Cell Death. In Cancer: Principles and Practice of Oncology; DeVita, V.T., Lawrence, T.S., Rosenberg, S.A., Eds.; Lippincott, Williams, and Wilkins: Philadelphia, PA, USA, 2008; Chapter 7, pp. 93–101.
[8]
Andrianasolo, E.H.; Haramaty, L.; Rosario-Passapera, R.; Bidle, K.; White, E.; Vetriani, C.; Falkowski, P.; Lutz, R. Ammonificins A and B, hydroxyethylamine chroman derivatives from a cultured marine hydrothermal vent bacterium, Thermovibrio ammonifican. J. Nat. Prod. 2009, 72, 1216–1219, doi:10.1021/np800726d.
[9]
Fahy, E.; Potts, B.C.M.; Faulkner, J. 6-bromotryptamine derivatives from the Gulf of California tunicate Didemnum candidum. J. Nat. Prod. 1991, 54, 564–569, doi:10.1021/np50074a032.
[10]
Ahlrichs, R.; Furche, F.; H？ttig, C.; Klopper, W.; Sierka, M.; Weigend, F. TURBOMOLE Software, version 5.10; COSMOlogic GmbH & Co. KG: Leverkusen, Germany, 2008.
[11]
Stetter, K.O.; K？nig, H.; Stackebrandt, E. Pyrodictium gen. nov., a new genus of submarine disc-shaped sulfur reducing archaebacteria growing optimally at 105 °C. Syst. Appl. Microbiol. 1983, 4, 535–551, doi:10.1016/S0723-2020(83)80011-3.
Holscher, D.; Reichert, M.; Gorls, H.; Ohlenschlager, O.; Bringmann, G.; Schneider, B. Monolaterol, the first configurationally assigned phenylphenalenone derivative with a stereogenic center at C-9, from Monochoria elata. J. Nat. Prod. 2006, 69, 1614–1617, doi:10.1021/np060192x.
[14]
Pecul, M.; Ruud, K.; Helgaker, T. Density functional theory calculation of electronic circular dichroism using London orbitals. Chem. Phys. Lett. 2004, 388, 110–119, doi:10.1016/j.cplett.2004.03.008.
[15]
Diedrich, C.; Grimme, S. Systematic investigation of modern quantum chemical methods to predict electronic circular dichroism spectra. J. Phys. Chem. 2003, 107, 2524–2539, doi:10.1021/jp0275802.
[16]
Antus, S.; Kurtan, T.; Juhász, L.; Kiss, L.; Hollósi, M.; Májer, Z.S. Chiroptical properties of 2,3-dihydrobenzo[b]furan and chromane chromophores in naturally occurring O-heterocycles. Chirality 2001, 13, 493–506, doi:10.1002/chir.1067.
[17]
Danial, N.; Korsmeyer, S. Cell death: Critical control points. Cell 2004, 116, 205–219, doi:10.1016/S0092-8674(04)00046-7.
[18]
Gelinas, C.; White, E. BH3-only proteins in control: Specificity regulates MCL-1 and BAK-mediated apoptosis. Genes Dev. 2005, 19, 1263–1268, doi:10.1101/gad.1326205.
[19]
Degenhardt, K.; White, E. A new generation of mouse models of cancer for translational research. Clin. Cancer Res. 2006, 12, 5274–5276, doi:10.1158/1078-0432.CCR-06-0500.
[20]
Fesik, S.W. Promoting apoptosis as a strategy for cancer drug discovery. Nat. Rev. Cancer 2005, 5, 876–885, doi:10.1038/nrc1736.
[21]
Degenhardt, K.S.R.; Chen, G.; Lindsten, T.; Thomson, C.; White, E. BAX and BAK mediate p53-independent suppression of tumorigenesis. J. Bio. Chem. 2002, 277, 14127–14134.
[22]
Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods 1983, 65, 55–63, doi:10.1016/0022-1759(83)90303-4.
[23]
Batista, J.M., Jr.; Lopes, A.A.; Ambr？sio, D.L.; Regasini, L.O.; Kato, M.J.; da Silva Bolzani, V.; Cicarelli, R.M.B.; Furlan, M. Natural chromenes and chromene derivatives as potential anti-trypanosomal agents. Biol. Pharm. Bull. 2008, 31, 538–540, doi:10.1248/bpb.31.538.
