title: Apoptosis-inducing effects of distichamine and narciprimine, rare alkaloids of the plant family Amaryllidaceae.
abstract: Several of the Amaryllidaceae alkaloids are known for their cytotoxic properties, of which the lycorine group representatives are prominent for potent and cell line specific antiproliferative activities. As a distinct niche within the lycorine group, the phenanthridones, exemplified by narciclasine and pancratistatin, have shown much promise as remarkably selective cytotoxic agents and are presently at various stages of development, with a clinical candidate likely to appear on the market within the next decade. The crinane group of the Amaryllidaceae has also spawned several molecules, such as crinamine and haemanthamine, with promising cytotoxic activities. In the present study, the β-crinane distichamine as well as the phenanthridone narciprimine, both rare constituents of the Amaryllidaceae, are revealed as novel antiproliferative agents. Apoptosis-inducing effects are demonstrated for distichamine in human acute lymphoblastic leukemia (CEM) cells. These findings provide further insights to the structural details of the apoptosis-inducing pharmacophores resident within both series of alkaloids.
authors.affiliation: Research Centre for Plant Growth and Development, School of Life Sciences, University of KwaZulu-Natal Pietermaritzburg, Private Bag X01, Scottsville 3209, South Africa.
authors.forename: Jerald J
authors.initials: JJ
authors.lastname: Nair
authors.forename: Lucie
authors.initials: L
authors.lastname: Rárová
authors.forename: Miroslav
authors.initials: M
authors.lastname: Strnad
authors.forename: Jaume
authors.initials: J
authors.lastname: Bastida
authors.forename: Johannes
authors.initials: J
authors.lastname: van Staden
mesh_terms: D047151:Amaryllidaceae Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D019668:Liliaceae / Q000737:chemistry*; D061986:MCF-7 Cells; D008968:Molecular Conformation; D010616:Phenanthrenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D047151:Amaryllidaceae Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D010616:Phenanthrenes; C573998:distichamine; C569972:narciprimine