Acetylcholinesterase inhibition within the lycorine series of Amaryllidaceae alkaloids

The plant family Amaryllidaceae occupies a privileged status within the botanical hierarchy due to its horticultural and ornamental appeal, as well as its widespread usage in the traditional medicinal practices of indigenous peoples across the globe. Of greater significance are the unique, structurally-diverse alkaloid constituents produced by members of the family, which has spawned several biologically significant molecules. In this regard, the Alzheimer's drug galanthamine has gained much prominence due to its selective and reversible inhibitory interaction with the enzyme acetylcholinesterase (AChE), of significance in the progression of neurodegeneration associated with Alzheimer's disease (AD). The lycorine series of compounds within the family have recently emerged as novel inhibitors of AChE, in some instances with higher levels of activity compared with the commercial drug galanthamine, making them attractive targets for natural product and synthetically-driven structure-activity relationship studies. This brief survey traces the emergence of lycorine compounds over the past decade as promising leads in the therapeutic approach towards AD and their possible future advancement onto the clinical stage.     

Amaryllidaceae and Sceletium alkaloids

This review covers the isolation, biological activity and chemical synthesis of Amaryllidaceae alkaloids and the structurally related Sceletium alkaloids. The literature from July 2001 to the end of 2002 is reviewed, and 61 references are cited.     

Amaryllidaceae and Sceletium alkaloids

This review covers the morphology, isolation, total synthesis and biological activity of the naturally occurring alkaloids isolated from the Amaryllidaceae family, as well as the structurally related Sceletium alkaloids.     

Amaryllidaceae and Sceletium alkaloids

Structurally diverse alkaloids, which show significant biological activities, are abundant in the plants of the family Amaryllidaceae. The latest progress on the isolation, identification, biological activity, and chemical synthesis of Amaryllidaceae alkaloids and the structurally close Sceletium alkaloids is summarized in this review.     

Amaryllidaceae and Sceletium alkaloids

A great number of natural products, especially alkaloids, which exhibit a range of biological activities including acetylcholinesterase inhibition and antineoplastic, cardiovascular and immunostimulatory activities, have been isolated from the plants of the Amaryllidaceae family. this review summarizes isolation, biological activity, and synthetic studies of these alkaloids. The primary biosynthetic pathways of each type of alkaloids are also proposed.     

Mass-spectrometric study of alkaloids of the lycorine type

Summary 1. The mass spectra of six alkaloids of the lycorine type (caranine, pluviine, lycorine, methylpseudolycorine, ungminorine, and galanthine) and four derivatives of these alkaloids have been studied.2. Three main directions of fragmentation of the molecular ions of the compounds studied have been established: the formation of the ion (M-1), the cleavage of ring B in the form of a retrodiene reaction, and the successive elimination of the substituents from rings B and C in the ion (M-1)⁺.Khimiya Frirodnykh Soedinenii, Vol. 4, No. 1, pp. 19–22, 1968     

Transformation of indole alkaloids—I : Conversion of oxindole alkaloids into indole alkaloids

Chemical conversion of some natural oxindoles (pteropodine, isopteropodine and isorhynchophylline) into the corresponding indole alkaloids has been made by way of a sequence of reactions which include formation of iminoethers of the natural oxindoles with Meerwein's reagent, reduction of the iminoethers to 2,3-seco-indoles and cyclization of 2,3-seco-indoles to the desired natural indole alkaloids. Sodium borohydride in acetic acid was found to be a specific reagent for the reduction of oxindole-iminoethers to 2,3-seco-indoles which were the key intermediates in these transformations. Yohimbine-oxindole iminoether was similarly converted to yohimbine and pseudoyohimbine. A number of by-products were obtained and their structures were elucidated.     

Mass spectra of dihydro derivatives of alkaloids of the lycorine type

Conclusions The mass spectra of dihydrolycorine, diacetylidhydrolycorine, dihydroungminorine, diacetyldihydroungminorine, and diacetyldihydroungminorinone have been studied.The fragmentation of these compounds differs from that of alkaloids of the lycorine type only by the absence of a retrodiene type of decomposition.Khimiya Prirodnykh Soedinenii, Vol. 4, No. 4, pp. 227–230, 1968     

Isolation and cholinesterase activity of Amaryllidaceae alkaloids from Nerine bowdenii

Amaryllidaceae species are known as ornamental plants. Some contain galanthamine, an acetylcholinesterase inhibitor. The chemical composition of the alkaloid extract of bulbs of Nerine bowdenii Watson has been analyzed by means of GC/MS. Twenty-two compounds were detected and nineteen of them identified, one of which was belladine. The alkaloid extract showed promising cholinesterase inhibitory activities against human blood acetylcholinesterase (HuAChE; IC50 = 87.9 +/- 3.5 microg/mL) and human plasma butyrylcholinesterase (HuBuChE; IC50 = 14.8 +/- 1.1 microg/mL). Belladine inhibited HuAChE and HuBuChE in a dose-dependent manner with IC50 values of 781 +/- 12.5 microM and 284.8 +/-4.2 microM, respectively.     

Comparison of different HPLC systems for analysis of galantamine and lycorine in various species of Amaryllidaceae family

Retention parameters of galantamine and lycorine standards were determined on different columns, i.e., octadecyl silica, SM C18, and strong cation-exchange (SCX) columns with different aqueous mobile phases. Retention of alkaloids was investigated on C18, SM C18 columns with mobile phase containing 5% MeCN, 20% acetate buffer at pH 3.5, and 0.025 ML^?1 diethylamine (DEA), and on SCX column with mobile phase containing 8% MeCN and phosphate buffer at pH 2.5. Better results were also obtained in ion-exchange chromatographic system. On the basis of results obtained in different chromatographic systems, simple, rapid, and sensitive high-performance liquid chromatography methods were developed for determining lycorine and galantamine in plant extracts from various species belonging to Amaryllidaceae family. Extracts were prepared from various parts of plants collected at different times of the growing season.     

Muscarine,imidazole, oxazole,thiazole, Amaryllidaceae and Sceletium alkaloids

A review with 136 references covers the literature from July 2000 to June 2001 on the isolation, bioactivities, and synthetic highlights of complex natural products including muscarine, imidazole, oxazole, thiazole, Amaryllidaceae and Sceletium alkaloids.