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Onnamide A

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Onnamide A
Names
Other names
(2S)-5-[(Diaminomethylene)amino]-2-({(2E,4E,6E,11R)-11-hydroxy-12-[(4S,4aS,6R,8S,8aR)-4-({(2S)-2-hydroxy-2-[(2R,5R,6R)-2-methoxy-5,6-dimethyl-4-methylenetetrahydro-2H-pyran-2-yl]acetyl}amino)-8-methox y-7,7-dimethylhexahydropyrano[3,2-d][1,3]dioxin-6-yl]-2,4,6-dodecatrienoyl}amino)pentanoic acid
Identifiers
3D model (JSmol)
ChemSpider
  • InChI=1S/C39H63N5O12/c1-23-21-39(52-7,56-25(3)24(23)2)32(47)34(48)44-35-31-30(53-22-54-35)33(51-6)38(4,5)28(55-31)20-26(45)16-13-11-9-8-10-12-14-18-29(46)43-27(36(49)50)17-15-19-42-37(40)41/h8-10,12,14,18,24-28,30-33,35,45,47H,1,11,13,15-17,19-22H2,2-7H3,(H,43,46)(H,44,48)(H,49,50)(H4,40,41,42)/b9-8 ,12-10 ,18-14 /t24-,25-,26-,27 ,28-,30 ,31 ,32 ,33-,35 ,39-/m1/s1
    Key: YWUNVHXKGMPHDM-XTDHNIAMSA-N
  • C[C@H]1[C@H](O[C@](CC1=C)([C@@H](C(=O)N[C@@H]2[C@@H]3[C@@H]([C@H](C([C@H](O3)C[C@@H](CCC/C=C/C=C/C=C/C(=O)N[C@@H](CCCNC(=N)N)C(=O)O)O)(C)C)OC)OCO2)O)OC)C
Properties
C39H63N5O12
Molar mass 793.956 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Onnamide A is a bioactive natural product found in Theonella swinhoei, a species of marine sponge whose genus is well known for yielding a diverse set of biologically active natural products, including the swinholides[1] and polytheonamides.[2] It bears structural similarities to the pederins, a family of compounds known to inhibit protein synthesis in eukaryotic cells. Onnamide A and its analogues have attracted academic interest due to their cytotoxicity and potential for combating the growth and proliferation of cancer cells.[3]

History

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Onnamide A was first isolated in 1988 from Theonella spp., a genus of marine sponges residing off the coast of Okinawa, Japan,[4] as part of a bioassay aimed at discovering novel marine natural products possessing antiviral activity. Eight analogues possessing similar structure, as well as cytotoxicity were reported in 1992.

Structure

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Onnamide A is a complex biomolecule with a 39 unique carbon atoms and 11 degrees of unsaturation. Its core contains three rings, two of which comprise a dimeric lactone structure. It contains a long side chain that has a three conjugated trans- olefins that connects to an amide bond, terminating in an arginine residue. The stereochemical assignments of onnamide A have been extensively characterized by experimental and advanced NMR studies.[4][5]

Biosynthesis

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proposed biosynthetic pathway for onnamide A via PKS-NRPS, showing polyketide and non-ribosomal polypeptide features

Genomic studies suggest strong homology with Ped genes, which encode the production of pederins, structurally similar compounds synthesized by bacterial endosymbionts of Paederus beetles. This suggests that onnamide A is actually the product of bacterial endosymbionts of the marine sponges from which the compound was first isolated. Thus, the biosynthetic pathway of onnamide A is envisioned to undertake analogous steps as those that lead to pederin, utilizing a prokaryotic PKS-NRPS system.[6]

Cytotoxicity

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Onnamide A inhibits protein synthesis in cell lines, leading to induction of stress-activated protein kinases apoptosis in the affected cell.[3] Its derivatives have been found to be highly toxic towards leukemic cells of the P388 cell line.[7]

See also

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Pederin

References

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  1. ^ Isao Kitagawa; Motomasa Kobayashi; Taketo Katori; Megumi Yamashita; Junichi Tanaka; Mitsunobu Doi; Toshimasa Ishida (1990). "Absolute stereostructure of swinholide A; a potent cytotoxic macrolide from the Okinawan marine sponge Theonella swinhoei". J. Am. Chem. Soc. 112 (9): 3710–3712. doi:10.1021/ja00165a094.
  2. ^ Micheal C. Wilson; Tetsushi Mori; Christian Rückert; Agustinus R. Uria; Maximilian J. Helf; Kentaro Takada, Christine Gernert; Ursula A. E. Steffens; Nina Heycke; Susanne Schmitt; Christian Rinke; Eric J. N. Helfrich; Alexander O. Brachmann; Cristian Gurgui; Toshiyuki Wakimoto; Matthias Kracht; Max Crüsemann; Ute Hentschel; Ikuro Abe; Shigeki Matsunaga; Jörn Kalinowski; Haruko Takeyama; Jörn Pielic (2014). "An environmental bacterial taxon with a large and distinct metabolic repertoire". Nature. 506 (14): 58–62. Bibcode:2014Natur.506...58W. doi:10.1038/nature12959. PMID 24476823.
  3. ^ a b Kun-Hyung Lee; Shinichi Nishimura; Shigeki Matsunaga; Nobuhiro Fusetani; Sueharu Horinouchi; Minoru Yoshida (2005). "Inhibition of protein synthesis and activation of stress-activated protein kinases by onnamide A and theopederin B, antitumor marine natural products". Cancer Sci. 96 (6): 357–364. doi:10.1111/j.1349-7006.2005.00055.x. PMC 11158271. PMID 15958059.
  4. ^ a b Shinichi Sakemi; Toshio Ichiba; Shigeo Kohmoto; Gabriel Saucy; Tatsuo Higa (1988). "Isolation and structure elucidation of onnamide A, a new bioactive metabolite of a marine sponge, Theonella sp". J. Am. Chem. Soc. 110 (14): 4851–4853. doi:10.1111/j.1349-7006.2005.00055.x. PMC 11158271. PMID 15958059. S2CID 30688113.
  5. ^ Yoshinari Miyata; Shigeki Matsunaga (2008). "Structure elucidation of 21,22-dihydroxyonnamides A1–A4 from the marine sponge Theonella swinhoei: an empirical rule to assign the relative stereochemistry of linear 1,5-diols". Tetrahedron Lett. 49 (44): 6334–6336. doi:10.1016/j.tetlet.2008.08.057.
  6. ^ Jörn Piel; Dequan Hui; Gaiping Wen; Daniel Butzke; Matthias Platzer; Nobuhiro Fusetani; Shigeki Matsunaga (2004). "Antitumor polyketide biosynthesis by an uncultivated bacterial symbiont of the marine sponge Theonella swinhoei". Proc. Natl. Acad. Sci. 101 (46): 16222–16227. Bibcode:2004PNAS..10116222P. doi:10.1073/pnas.0405976101. PMC 528957. PMID 15520376.
  7. ^ Shigeki Matsunaga; Nobuhiro Fusetani; Youichi Nakao (1992). "Eight New Cytotoxic Metabolites Closely Related to Onnamide A from Two Marine Sponges of the Genus Theonella". Tetrahedron. 48 (39): 8369–8376. doi:10.1016/S0040-4020(01)86585-6.
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