Laucysteinamide A

Last updated
Laucysteinamide A
Laucysteinamide A.svg
Chemical structure of laucysteinamide A
Names
Preferred IUPAC name
(12E)-N-Methyl-13-[(2R)-2-methyl-4,5-dihydro-1,3-thiazol-4-yl]-N-[(1E)-penta-1,4-dien-1-yl]tridec-12-enamide
Identifiers
3D model (JSmol)
ChemSpider
PubChem CID
  • InChI=1S/C23H38N2OS/c1-4-5-16-19-25(3)23(26)18-15-13-11-9-7-6-8-10-12-14-17-22-20-27-21(2)24-22/h4,14,16-17,19,22H,1,5-13,15,18,20H2,2-3H3/b17-14+,19-16+/t22-/m1/s1
    Key: AYRWEQNQZDTIDT-GIWCFZTQSA-N
  • CC1=N[C@@H](CS1)/C=C/CCCCCCCCCCC(=O)N(C)/C=C/CC=C
Properties
C23H38N2OS
Molar mass 390.63 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Laucysteinamide A (LcA) is a marine natural product isolated from a cyanobacterium, Caldora penicillata. [1]

It is structurally related to other marine cyanobacterial metabolites such as somocystinamide A [2] and curacin A, which have inspired extensive investigations into their use as a lead for anticancer therapies. [3] [4] [5] [6] Its biological activity profile has not been fully evaluated due to decomposition of the natural sample. However, it has shown moderate cytotoxicity against H460 human lung cancer cells. [1]

In order to examine the possibility that LcA's true bioactivity was diminished by solubility issues, Taylor et al. chemically synthesize d LcA. [7] This synthetic sample was incorporated into an emulsifier PEG400 and tested for its cytotoxicity against H460 cells. This sample did not show any more activity than the natural sample, implying that LcA only has moderate cytotoxicity. In addition, simple enamide analogs showed no activity. [7] This work implies that the exceptional antiproliferative activity of somocystinamide A arises from the dimeric nature of its structure and not from the enamide moiety.

See also

References

  1. 1 2 Zhang, Chen; Naman, C. Benjamin; Engene, Niclas; Gerwick, William H. (April 2017). "Laucysteinamide A, a Hybrid PKS/NRPS Metabolite from a Saipan Cyanobacterium, cf. Caldora penicillata". Marine Drugs. 15 (4): 121. doi: 10.3390/md15040121 . PMC   5408267 . PMID   28420100.
  2. ↑ Nogle, Lisa M.; Gerwick, William H. (2002-04-01). "Somocystinamide A, a Novel Cytotoxic Disulfide Dimer from a Fijian Marine Cyanobacterial Mixed Assemblage" . Organic Letters. 4 (7): 1095–1098. doi:10.1021/ol017275j. ISSN   1523-7060. PMID   11922791.
  3. ↑ Wrasidlo, Wolf; Mielgo, Ainhoa; Torres, Vicente A.; Barbero, Simone; Stoletov, Konstantin; Suyama, Takashi L.; Klemke, Richard L.; Gerwick, William H.; Carson, Dennis A.; Stupack, Dwayne G. (2008-02-19). "The marine lipopeptide somocystinamide A triggers apoptosis via caspase 8". Proceedings of the National Academy of Sciences. 105 (7): 2313–2318. Bibcode:2008PNAS..105.2313W. doi: 10.1073/pnas.0712198105 . ISSN   0027-8424. PMC   2268133 . PMID   18268346.
  4. ↑ Suyama, Takashi L.; Gerwick, William H. (2008-10-16). "Stereospecific Total Synthesis of Somocystinamide A". Organic Letters. 10 (20): 4449–4452. doi:10.1021/ol8016947. ISSN   1523-7060. PMC   3227555 . PMID   18788741.
  5. ↑ Verdier-Pinard, P.; Lai, J. Y.; Yoo, H. D.; Yu, J.; Marquez, B.; Nagle, D. G.; Nambu, M.; White, J. D.; Falck, J. R.; Gerwick, W. H.; Day, B. W. (January 1998). "Structure-activity analysis of the interaction of curacin A, the potent colchicine site antimitotic agent, with tubulin and effects of analogs on the growth of MCF-7 breast cancer cells". Molecular Pharmacology. 53 (1): 62–76. doi:10.1124/mol.53.1.62. ISSN   0026-895X. PMID   9443933.
  6. ↑ Wipf, Peter; Reeves, Jonathan T.; Day, Billy W. (2004). "Chemistry and biology of curacin A". Current Pharmaceutical Design. 10 (12): 1417–1437. doi:10.2174/1381612043384853. ISSN   1381-6128. PMID   15134491.
  7. 1 2 Taylor, Kimberly S.; Zhang, Chen; Glukhov, Evgenia; Gerwick, William H.; Suyama, Takashi L. (2021-02-26). "Total Synthesis of Laucysteinamide A, a Monomeric Congener of Somocystinamide A" . Journal of Natural Products. 84 (3): 865–870. doi:10.1021/acs.jnatprod.0c01317. ISSN   0163-3864. PMID   33635664. S2CID   232065030.


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