Structure-activity studies on the lycorine pharmacophore: A potent inducer of apoptosis in human leukemia cells.
The direct chemoselective differential functionalization of the ring-C hydroxyl groups present in the Amaryllidaceae alkaloid lycorine is described allowing for selective manipulation of the 1,2-hydroxyl groups. A mini-library comprised of synthetic and natural lycorane alkaloids was prepared and their apoptosis-inducing activity investigated in human leukemia (Jurkat) cells. Further insights into the nature of this interesting apoptosis-inducing pharmacophore are described, including the requirement of both free hydroxyl groups in ring-C.
McNulty
James
J
Department of Chemistry, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4M1. jmcnult@mcmaster.ca
Nair
Jerald J
JJ
Bastida
Jaume
J
Pandey
Siyaram
S
Griffin
Carly
C
D047151:Amaryllidaceae Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D019169:Jurkat Cells; D015394:Molecular Structure; D010617:Phenanthridines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D047151:Amaryllidaceae Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D010617:Phenanthridines; C015330:lycorine