Symplocamide A

Symplocamide A
Names
	IUPAC name N1-[(2S,5S,8S,11R,12S,15S,18S,21R)-5-(3-bromo-4-methoxybenzyl)-2-[(2S)-butan-2-yl]-15-[3-(carbamoylamino)propyl]-21-hydroxy-4,11-dimethyl-3,6,9,13,16,22-hexaoxo-8-(propan-2-yl)-10-oxa-1,4,7,14,17-pentaazabicyclo[16.3.1]docos-12-yl]-N2-butanoyl-L-glutamamide
Identifiers
CAS Number	1007391-44-7 ;
3D model (JSmol)	Interactive image;
ChEMBL	ChEMBL436840;
ChemSpider	23314421 ;
PubChem CID	44448139;
CompTox Dashboard (EPA)	DTXSID40659157 ;
	InChI InChI=1S/C46H71BrN10O13/c1-9-12-34(59)51-29(15-18-33(48)58)40(62)55-37-25(6)70-45(67)36(23(3)4)54-41(63)31(22-26-14-17-32(69-8)27(47)21-26)56(7)44(66)38(24(5)10-2)57-35(60)19-16-30(43(57)65)53-39(61)28(52-42(37)64)13-11-20-50-46(49)68/h14,17,21,23-25,28-31,35-38,60H,9-13,15-16,18-20,22H2,1-8H3,(H2,48,58)(H,51,59)(H,52,64)(H,53,61)(H,54,63)(H,55,62)(H3,49,50,68)/t24-,25 ,28-,29-,30-,31-,35 ,36-,37-,38-/m0/s1 Key: XFQCUAOQRAZAJB-APLIVAFESA-N;
	SMILES CCCC(=O)N[C@@H](CCC(=O)N)C(=O)N[C@H]1[C@H](OC(=O)[C@@H](NC(=O)[C@@H](N(C(=O)[C@@H](N2[C@@H](CC[C@@H](C2=O)NC(=O)[C@@H](NC1=O)CCCNC(=O)N)O)[C@@H](C)CC)C)Cc3ccc(c(c3)Br)OC)C(C)C)C;
Properties
Chemical formula	C46H71BrN10O13
Molar mass	1052.035 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Symplocamide A is a newly discovered (2008) 3-amino-6-hydroxy-2-piperidone (Ahp) cyclodepsipeptide that has been isolated from a marine cyanobacteria in Papua New Guinea, which has only been identified at the genus level (Symploca).^[2] Cyanobacteria, both freshwater and marine, are known as producers of diverse protease inhibitors that may be used to treat diseases, such as HIV, and some forms of cancer. Research on symplocamide A has shown that it is a strong serine protease inhibitor and has a high level of cytotoxicity to cancer cells when used in vitro.^[3] As of the time of this writing, its use as a treatment on human participants has not been done and future study will have to be done before any human testing can be commenced.

Origin

Symplocamide A has only recently been discovered when scientists were looking for various marine cyanobacterium in order to extract possible protease inhibitors not seen in freshwater cyanobacterium. It was obtained from Symploca sp. in Papua New Guinea, and the genus has not been recorded in the literature. Using nuclear magnetic resonance (NMR), the molecular formula (C₄₆H₇₁BrN₁₀O₁₃) and structure were elucidated.^[3] More data will need to be gathered, as without a genus being described by the discovery of symplocamide A, recreation of the data cannot be confirmed.

Biological activities

Symplocamide A is an extremely potent cytotoxin, which has shown potential for treating H460 lung cancer and neuro-2A neuroblastoma cells with IC₅₀ values of 40 nM and 29 nM, respectively.^[4] Symplocamide A has also been determined to be a potent protease inhibitor which may be used for the treatment of infectious diseases, such as HIV and HCV, if it is similar to other protease inhibitors that have been used before as treatments.^[3]

References

^ Chemspider http://www.chemspider.com/Chemical-Structure.23314421.html
^ Stolze, Sara C.; Michael Meltzer; Michael Ehrmann; Markus Kaiser (27 September 2010). "Solid phase total synthesis of the 3-amino-6-hydroxy-2-piperidone (Ahp) cyclodepsipeptide and protease inhibitor Symplocamide A". Chemical Communications. 46 (46): 8857–8859. doi:10.1039/c0cc02889d. PMID 20967347. S2CID 36924580.
^ ^a ^b ^c Linington, Roger G.; Daniel J. Edwards; Cynthia F. Shuman; Kerry L. McPhail; Teatulohi Matainaho; William H. Gerwick (2007). "Symplocamide A, a potent cytotoxin and chymotrypsin inhibitor from the marine cyanobacterium Symploca sp". Journal of Natural Products. 71 (1): 22–27. doi:10.1021/np070280x. PMC 2832912. PMID 18163584.
^ Kinghorn, A. Douglas; Young-Won Chin; Steven M. Swanson (March 2009). "Discovery of natural products anticancer agents from biodiverse organisms". Current Opinion in Drug Discovery & Development. 12 (2): 189–196. PMC 2877274. PMID 19333864.

[Chemspider-1] Chemspider http://www.chemspider.com/Chemical-Structure.23314421.html

[2] Stolze, Sara C.; Michael Meltzer; Michael Ehrmann; Markus Kaiser (27 September 2010). "Solid phase total synthesis of the 3-amino-6-hydroxy-2-piperidone (Ahp) cyclodepsipeptide and protease inhibitor Symplocamide A". Chemical Communications. 46 (46): 8857–8859. doi:10.1039/c0cc02889d. PMID 20967347. S2CID 36924580.

[Linington_2007_22–27-3] Linington, Roger G.; Daniel J. Edwards; Cynthia F. Shuman; Kerry L. McPhail; Teatulohi Matainaho; William H. Gerwick (2007). "Symplocamide A, a potent cytotoxin and chymotrypsin inhibitor from the marine cyanobacterium Symploca sp". Journal of Natural Products. 71 (1): 22–27. doi:10.1021/np070280x. PMC 2832912. PMID 18163584.

[4] Kinghorn, A. Douglas; Young-Won Chin; Steven M. Swanson (March 2009). "Discovery of natural products anticancer agents from biodiverse organisms". Current Opinion in Drug Discovery & Development. 12 (2): 189–196. PMC 2877274. PMID 19333864.

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