title: Structure activity studies on the crinane alkaloid apoptosis-inducing pharmacophore.
abstract: 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.
authors.affiliation: Department of Chemistry, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4M1, Canada. jmcnult@mcmaster.ca
authors.forename: James
authors.initials: J
authors.lastname: McNulty
authors.forename: Jerald J
authors.initials: JJ
authors.lastname: Nair
authors.forename: Jaume
authors.initials: J
authors.lastname: Bastida
authors.forename: Siyaram
authors.initials: S
authors.lastname: Pandey
authors.forename: Carly
authors.initials: C
authors.lastname: Griffin
mesh_terms: 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
chemical_list: D047151:Amaryllidaceae Alkaloids; D010617:Phenanthridines; D010936:Plant Extracts; C504763:crinane; C462104:hemanthamine; C411129:crinamine; D053148:Caspase 3