n-methylcytisine and cytisine

Quinolizidine alkaloids exhibit various forms of biological activity. A lot of them were found in the

Topics: Alkaloids; Antineoplastic Agents, Phytogenic; Azocines; Cell Survival; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Humans; MCF-7 Cells; Neoplasms; Plant Extracts; Quinolizines; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

The first direct synthesis of 3-

Topics: Aldehydes; Alkaloids; Azocines; Formates; Hydroxylamines; Magnetic Resonance Spectroscopy; Nitrogen Oxides; Oximes; Pyridones; Quinolizines

Alkaloid contents of leaf and seed samples of eight species of Sophora native to New Zealand, plus Sophora cassioides from Chile are reported. Fifty-six leaf and forty-two seed samples were analysed for alkaloid content by proton nuclear magnetic resonance spectroscopy, which showed major alkaloids as cytisine, N-methyl cytisine and matrine. GC analyses quantified these and identified further alkaloid components. The alkaloids identified were cytisine, sparteine, and matrine-types common to Sophora from other regions of the world. Cytisine, N-methyl cytisine, and matrine were generally the most abundant alkaloids across all species with seeds containing the highest concentrations of alkaloids. However, there was no clear taxonomic grouping based on alkaloid composition. A quantitative analysis of various parts of two Sophora microphylla trees showed that the seeds were the richest source of alkaloids (total 0.4-0.5% DM), followed by leaf and twig (0.1-0.3%) and then bark (0.04-0.06%), with only low amounts (<0.02%) found in the roots. This study represents the most comprehensive phytochemical investigation of New Zealand Sophora species to date and presents data for three species of Sophora for which no prior chemistry has been reported.

Topics: Alkaloids; Azocines; Chile; Drugs, Chinese Herbal; Matrines; Molecular Structure; New Zealand; Plant Leaves; Plant Roots; Quinolizines; Seeds; Sophora

(-)-Cytisine and its derivatives are promising alkaloids in the development of new drugs for the treatment of disorders of the central nervous system (CNS). Electron ionization (EI) mass spectral fragmentations of cytisine (1), N-methylcytisine (2), N-ethylcytisine (3), N-acetylcytisine (4), N-propionylcytisine (5) and N-benzoylcytisine (6) have been investigated. Detailed fragmentation pathways have been identified for all significant ions, including a few characteristic fragment ions. The principal fragmentation routes of compounds 1-6 have been determined on the basis of EI low-resolution, high-resolution and B2/E linked scans as well as linked scans at constant B/E.

Topics: Alkaloids; Alkylation; Amides; Amination; Azocines; Quinolizines; Spectrometry, Mass, Electrospray Ionization

Cytisine (cy) is a potent and competitive partial agonist at alpha4 subunit-containing nicotinic acetylcholine (nACh) receptors while at homomeric alpha7-nACh receptors it behaves as a full agonist with a relatively lower potency. In the present study, we assessed the effects of bromination or iodination of the pyridone ring of cy and N-methylcytisine (N-Me-cy) on the effects of these compounds on recombinant human (h) alpha7, halpha4beta2 and halpha4beta4 nACh receptors expressed in clonal cell lines and Xenopus oocytes. Halogenation at C(3) of cy or N-Me-cy usually brings about a marked increase in both affinity and efficacy at halpha7, halpha4beta2 and halpha4beta4 nACh, the extent of which depends on whether the halogen is bromine or iodine, and upon receptor subtype. The effects of halogenation at C(5) are strongly influenced by the specific halogen substituent so that bromination causes a decrease in both affinity and efficacy while iodination decreases affinity but its effects on efficacy range from a decrease (halpha7, halpha4beta4 nACh receptors) to a marked increase (halpha4beta2 nACh receptors). Based on these findings, which differ from those showing that neither the affinity nor efficacy of nicotine, 3-(2-azetidinylmethoxy)-pyridine or epibatidine are greatly affected by halogenation, dehalogenation or halogen exchange at equivalent positions, we suggest that cy, N-Me-cy and their halo-isosteres bind to neuronal nACh receptors in a different orientation allowing the halogen atom to interact with a hydrophobic halogen-accepting region within the predominantly hydrophobic agonist-binding pocket of the receptors.

Topics: Alkaloids; Animals; Azocines; Bromine; Cell Line; Humans; Iodine; Nicotinic Agonists; Patch-Clamp Techniques; Quinolizines; Radioligand Assay; Receptors, Nicotinic; Recombinant Proteins; Structure-Activity Relationship; Xenopus laevis