McNulty James, Nair Jerald J, Singh Mohini, Crankshaw Denis J, Holloway Alison C, Bastida Jaume
Department of Chemistry and Chemical Biology, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4M1, Canada.
Nat Prod Commun. 2010 Aug;5(8):1195-200.
A mini-panel of semi-synthetic analogs of the Amaryllidaceae alkaloid lycorine was screened for cytochrome P450 3A4 (CYP3A4) inhibitory activity, the most potent of which exhibited inhibition as low as 0.21 microM. Elements of this novel pharmacophore unravelled include bulky lipophilic substitution at C2 in conjunction with a small hydrogen bond donor/acceptor at C1, or bulky electron-rich substitution at C1 in conjunction with a vicinal hydrogen bond donor/acceptor.
