Photohuperzine A-A new photoisomer of huperzine A: structure elucidation, formation kinetics and activity assessment.
A new photoisomer of the promising "anti-Alzheimer" drug candidate (+/-) huperzine A is described. The new substance was formed via a photoisomerization reaction and was found to be 1-amino-13-ethylidene-11-methyl-6-aza-tetracyclo-[7.3.1.0(2.7).0(4.7)]-trideca-2,10-diene-5-one using NMR analysis. The kinetics of its formation was studied and proven to be of first-order. The described photoisomer showed a significant loss in activity, being more than 100 times less active than (-) huperzine A itself. The new substance was named photohuperzine A, referring to its photopyridone substructure.
VU University Amsterdam, Faculty of Sciences, BioMolecular Analysis Group, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
Lygia Azevedo
LA
Marques
Martin
M
Giera
Frans J J
FJ
de Kanter
Wilfried M A
WM
Niessen
Henk
H
Lingeman
Hubertus
H
Irth
D000470:Alkaloids; D001681:Biological Assay; D002138:Calibration; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000378:metabolism*; D002853:Chromatography, Liquid; D007700:Kinetics; D013058:Mass Spectrometry; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D055668:Photochemical Processes / Q000528:radiation effects*; D012015:Reference Standards; D012717:Sesquiterpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D012717:Sesquiterpenes; C549542:photohuperzine A; C050426:huperzine A