Apoptosis-inducing effects of distichamine and narciprimine, rare alkaloids of the plant family Amaryllidaceae

• Published in: Bioorganic & medicinal chemistry letters 2012-10, Vol.22 (19), p.6195-6199
• Main Authors: Nair, Jerald J., Rárová, Lucie, Strnad, Miroslav, Bastida, Jaume, van Staden, Johannes
• Format: Article
• Language: English
• Subjects: Alkaloid; Amaryllidaceae; Amaryllidaceae Alkaloids - chemistry; Amaryllidaceae Alkaloids - isolation & purification; Amaryllidaceae Alkaloids - pharmacology; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Cell Line; Cell Survival - drug effects; chemistry; cytotoxicity; Distichamine; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; HeLa Cells; Humans; Indexing in process; Liliaceae - chemistry; lycorine; lymphocytic leukemia; markets; MCF-7 Cells; Medical sciences; Molecular Conformation; Narciprimine; pharmacology; Pharmacology. Drug treatments; Phenanthrenes - chemistry; Phenanthrenes - isolation & purification; Phenanthrenes - pharmacology; Stereoisomerism; Structure-Activity Relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.08.005

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.