Desformylflustrabromine

Desformylflustrabromine
Clinical data
ATC code	none;
Identifiers
	IUPAC name 2-[6-bromo-2-(2-methylbut-3-en-2-yl)-1H-indol-3-yl]-N-methylethanamine;
CAS Number	474657-72-2 ;
PubChem CID	637026;
ChemSpider	552693 ;
Chemical and physical data
Formula	C16H21BrN2
Molar mass	321.254 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C=CC(C)(C)c2nc1cc(Br)ccc1c2CCNC;
	InChI InChI=1S/C16H21BrN2/c1-5-16(2,3)15-13(8-9-18-4)12-7-6-11(17)10-14(12)19-15/h5-7,10,18-19H,1,8-9H2,2-4H3 ; Key:GQHSCJUTJKLZPX-UHFFFAOYSA-N ;
	(what is this?) (verify)

Desformylflustrabromine (dFBr) is a tryptamine derivative which was first isolated as an active metabolite of the marine bryozoan Flustra foliacea.^[1]

Bioactivity

dFBr has been identified as a novel positive allosteric modulator of neuronal nicotinic acetylcholine receptor with sub-type specificity for heteromeric receptor with no effect on homomeric sub-type.^[2] A recent study has been published which describes the synthesis of water-soluble salts of dFBr and its action has been confirmed as selective potentiator of α4β2 nicotinic acetylcholine receptor responses by using two-electrode voltage clamp whole cell recordings.^[3] In the year 2002 it was reported that dFBr was cytotoxic on human colon cancer cell line HCT-116.^[4] Desformylflustrabromine has also been found to be a positive allosteric modulator for the α2β2 subtype of neuronal nicotinic acetylcholine receptor. Additionally it relieves the inhibition of both α2β2 and α4β2 Nicotinic Acetylcholine Receptors by β-Amyloid (1–42) Peptide.^[5] Thus Desformylflustrabromine can potentially be used in the treatment of Alzheimer's disease. Many of the deconstructed analogs of dFBr are reported to have a potentiating effect on the α4β2 receptors.^[6]

References

^ Peters, Lars; Wright, Anthony D.; Kehraus, Stefan; Gündisch, Daniela; Tilotta, M. C.; König, Gabriele M. (October 2004). "Prenylated indole alkaloids from Flustra foliacea with subtype specific binding on NAChRs". Planta Med. 70 (10): 883–6. doi:10.1055/s-2004-832610. PMID 15490312.
^ Sala, Francisco; Mulet, José; Reddy, Krishna P.; Bernal, José Antonio; Wikman, Philip; Valor, Luis Miguel; Peters, Lars; König, Gabriele M.; Criado, Manuel (January 2005). "Potentiation of human alpha4beta2 neuronal nicotinic receptors by a Flustra foliacea metabolite". Neurosci. Lett. 373 (2): 144–9. doi:10.1016/j.neulet.2004.10.002. PMID 15567570.
^ Kim, Jin-Sung; Padnya, Anshul; Weltzin, Maegan; Edmonds, Brian W.; Schulte, Marvin K.; Glennon, Richard A. (Sep 2007). "Synthesis of desformylflustrabromine and its evaluation as an alpha4beta2 and alpha7 nACh receptor modulator". Bioorganic and Medicinal Chemistry Letters. 17 (17): 4855–60. doi:10.1016/j.bmcl.2007.06.047. PMC 3633077. PMID 17604168.
^ Lysek, N; Rachor, E; Lindel, T (2002). "Isolation and structure elucidation of deformylflustrabromine from the North Sea bryozoan Flustra foliacea". Z. Naturforsch. C. 57 (11–12): 1056–61. PMID 12562094.
^ Pandya, Anshul; Yakel, Jerrel L. (September 2011). "Allosteric modulator Desformylflustrabromine relieves the inhibition of α2β2 and α4β2 nicotinic acetylcholine receptors by β-amyloid(1-42) peptide". J. Mol. Neurosci. 45 (1): 42–7. doi:10.1007/s12031-011-9509-3. PMC 3235685. PMID 21424792.
^ German, Nadezhda; Kim, Jin-Sung; Jain, Atul; Dukat, Malgorzata; Pandya, Anshul; Ma, Yilong; Weltzin, Maegan; Schulte, Marvin K.; Glennon, Richard A. (October 2011). "Deconstruction of the α4β2 nicotinic acetylcholine receptor positive allosteric modulator desformylflustrabromine". J. Med. Chem. 54 (20): 7259–67. doi:10.1021/jm200834x. PMC 3200116. PMID 21905680.

This pharmacology-related article is a stub. You can help Wikipedia by expanding it.

[1] Peters, Lars; Wright, Anthony D.; Kehraus, Stefan; Gündisch, Daniela; Tilotta, M. C.; König, Gabriele M. (October 2004). "Prenylated indole alkaloids from Flustra foliacea with subtype specific binding on NAChRs". Planta Med. 70 (10): 883–6. doi:10.1055/s-2004-832610. PMID 15490312.

[2] Sala, Francisco; Mulet, José; Reddy, Krishna P.; Bernal, José Antonio; Wikman, Philip; Valor, Luis Miguel; Peters, Lars; König, Gabriele M.; Criado, Manuel (January 2005). "Potentiation of human alpha4beta2 neuronal nicotinic receptors by a Flustra foliacea metabolite". Neurosci. Lett. 373 (2): 144–9. doi:10.1016/j.neulet.2004.10.002. PMID 15567570.

[3] Kim, Jin-Sung; Padnya, Anshul; Weltzin, Maegan; Edmonds, Brian W.; Schulte, Marvin K.; Glennon, Richard A. (Sep 2007). "Synthesis of desformylflustrabromine and its evaluation as an alpha4beta2 and alpha7 nACh receptor modulator". Bioorganic and Medicinal Chemistry Letters. 17 (17): 4855–60. doi:10.1016/j.bmcl.2007.06.047. PMC 3633077. PMID 17604168.

[4] Lysek, N; Rachor, E; Lindel, T (2002). "Isolation and structure elucidation of deformylflustrabromine from the North Sea bryozoan Flustra foliacea". Z. Naturforsch. C. 57 (11–12): 1056–61. PMID 12562094.

[5] Pandya, Anshul; Yakel, Jerrel L. (September 2011). "Allosteric modulator Desformylflustrabromine relieves the inhibition of α2β2 and α4β2 nicotinic acetylcholine receptors by β-amyloid(1-42) peptide". J. Mol. Neurosci. 45 (1): 42–7. doi:10.1007/s12031-011-9509-3. PMC 3235685. PMID 21424792.

[6] German, Nadezhda; Kim, Jin-Sung; Jain, Atul; Dukat, Malgorzata; Pandya, Anshul; Ma, Yilong; Weltzin, Maegan; Schulte, Marvin K.; Glennon, Richard A. (October 2011). "Deconstruction of the α4β2 nicotinic acetylcholine receptor positive allosteric modulator desformylflustrabromine". J. Med. Chem. 54 (20): 7259–67. doi:10.1021/jm200834x. PMC 3200116. PMID 21905680.

[1]

[2]

[3]

[4]

[5]

[6]