Acetylcholinesterase-inhibiting alkaloids from Zephyranthes concolor

• Published in: Molecules (Basel, Switzerland) Switzerland), 2011-11, Vol.16 (11), p.9520-9533
• Main Authors: Reyes-Chilpa, Ricardo, Berkov, Strahil, Hernández-Ortega, Simón, Jankowski, Christopher K, Arseneau, Sebastien, Clotet-Codina, Imma, Esté, José A, Codina, Carles, Viladomat, Francesc, Bastida, Jaume
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase - metabolism; alkaloids; Alkaloids - chemistry; Alkaloids - metabolism; Alkaloids - pharmacology; Alzheimer's disease; amaryllidaceae; Amaryllidaceae Alkaloids - chemistry; Amaryllidaceae Alkaloids - metabolism; Amaryllidaceae Alkaloids - pharmacology; Animals; Antiviral Agents - chemistry; Antiviral Agents - metabolism; Antiviral Agents - pharmacology; Cell Line; chlidanthine; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - metabolism; Cholinesterase Inhibitors - pharmacology; Electronic mail systems; Electrophorus; Galantamine - chemistry; Galantamine - metabolism; Galantamine - pharmacology; HIV; HIV-1 - drug effects; Human immunodeficiency virus; Humans; Hydrogen Bonding; Liliaceae - anatomy & histology; Liliaceae - chemistry; Molecular Sequence Data; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Plant Extracts - chemistry; X-Ray Diffraction; Zephyranthes concolor
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules16119520

The bulbs and aerial parts of Zephyranthes concolor (Lindl.) Benth. & Hook. f. (Amaryllidaceae), an endemic species to Mexico, were found to contain the alkaloids chlidanthine, galanthamine, galanthamine N-oxide, lycorine, galwesine, and epinorgalanthamine. Since currently only partial and low resolution (1)H-NMR data for chlidanthine acetate are available, and none for chlidanthine, its 1D and 2D high resolution (1)H- and (13)C-NMR spectra were recorded. Unambiguous assignations were achieved with HMBC, and HSQC experiments, and its structure was corroborated by X-ray diffraction. Minimum energy conformation for structures of chlidanthine, and its positional isomer galanthamine, were calculated by molecular modelling. Galanthamine is a well known acetylcholinesterase inhibitor; therefore, the isolated alkaloids were tested for this activity. Chlidanthine and galanthamine N-oxide inhibited electric eel acetylcholinesterase (2.4 and 2.6 × 10(-5) M, respectively), indicating they are about five times less potent than galanthamine, while galwesine was inactive at 10(-3) M. Inhibitory activity of HIV-1 replication, and cytotoxicity of the isolated alkaloids were evaluated in human MT-4 cells; however, the alkaloids showed poor activity as compared with standard anti-HIV drugs, but most of them were not cytotoxic.