Structure activity studies on the crinane alkaloid apoptosis-inducing pharmacophore.
The apoptosis-inducing ability of alpha-ethano bridged crinane alkaloids was investigated using natural and semi-synthetic derivatives uncovering novel structural requirements of this cytotoxic pharmacophore. An alpha-ethano bridge is required; an alpha- or beta-methoxy or hydroxyl H-bond acceptor are all tolerated at C-3; a small substituent (H, or OH) alone is tolerated at C-11; and a C-1 to C-2 double bond is shown to modulate, but is not a requirement for, apoptosis-inducing activity.
McNulty
James
J
Department of Chemistry, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4M1, Canada. jmcnult@mcmaster.ca
Nair
Jerald J
JJ
Bastida
Jaume
J
Pandey
Siyaram
S
Griffin
Carly
C
D047151:Amaryllidaceae Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D006865:Hydrogenation; D019169:Jurkat Cells; D010617:Phenanthridines / Q000737:chemistry / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry; D013329:Structure-Activity Relationship
D047151:Amaryllidaceae Alkaloids; D010617:Phenanthridines; D010936:Plant Extracts; C504763:crinane; C462104:hemanthamine; C411129:crinamine; D053148:Caspase 3