Selective cytochrome P450 3A4 inhibitory activity of Amaryllidaceae alkaloids.
A library of natural and semi-synthetic Amaryllidaceae alkaloids was screened for cytochrome P450 3A4 (CYP3A4) inhibitory activity. Of the crinane, lycorane and galanthamine representatives examined two semi-synthetic silylated lycorane analogues, accessed via a chemoselective silylation strategy from lycorine, and the natural compound narciclasine exhibited low micromolar activities. Important pharmacological features uncovered include the lack of CYP3A4 inhibitory activity seen for galanthamine and the selective activity that is seen with narciclasine over pancratistatin.
McNulty
James
J
Department of Chemistry, McMaster University, 1280 Main Street West, Hamilton, Ont., Canada L8S 4M1. jmcnult@mcmaster.ca
Nair
Jerald J
JJ
Singh
Mohini
M
Crankshaw
Denis J
DJ
Holloway
Alison C
AC
Bastida
Jaume
J
D047151:Amaryllidaceae Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors; D005702:Galantamine / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D010617:Phenanthridines / Q000737:chemistry / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000494:pharmacology
D047151:Amaryllidaceae Alkaloids; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010617:Phenanthridines; D054852:Small Molecule Libraries; C412290:lycorane; D005702:Galantamine; C010753:narciclasine; C044997:pancratistatin; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C015330:lycorine