Amaryllidaceae Alkaloids Belonging to Different Structural Subgroups Display Activity against Apoptosis-Resistant Cancer Cells

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2010-07, Vol.73 (7), p.1223-1227
• Main Authors: Van Goietsenoven, Gwendoline, Andolfi, Anna, Lallemand, Benjamin, Cimmino, Alessio, Lamoral-Theys, Delphine, Gras, Thierry, Abou-Donia, Amina, Dubois, Jacques, Lefranc, Florence, Mathieu, Véronique, Kornienko, Alexander, Kiss, Robert, Evidente, Antonio
• Format: Article
• Language: English
• Subjects: Amaryllidaceae Alkaloids - chemistry; Amaryllidaceae Alkaloids - isolation & purification; Amaryllidaceae Alkaloids - pharmacology; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Biological and medical sciences; Drug Resistance, Neoplasm - drug effects; Drug Screening Assays, Antitumor; General pharmacology; Humans; Medical sciences; Molecular Structure; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Phenanthridines - chemistry; Phenanthridines - isolation & purification; Phenanthridines - pharmacology
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np9008255

Fifteen Amaryllidaceae alkaloids (1−15) were evaluated for their antiproliferative activities against six distinct cancer cell lines. Several of these natural products were found to have low micromolar antiproliferative potencies. The log P values of these compounds did not influence their observed activity. When active, the compounds displayed cytostatic, not cytotoxic activity, with the exception of pseudolycorine (3), which exhibited cytotoxic profiles. The active compounds showed similar efficacies toward cancer cells irrespective of whether the cell lines were responsive or resistant to proapoptotic stimuli. Altogether, the data from the present study revealed that lycorine (1), amarbellisine (6), haemanthamine (14), and haemanthidine (15) are potentially useful chemical scaffolds to generate further compounds to combat cancers associated with poor prognoses, especially those naturally resistant to apoptosis, such as glioblastoma, melanoma, non-small-cell lung, and metastatic cancers.