Amaryllidaceae alkaloids biological activities

The present survey is divided into three sections. The first reviews only die completed syntheses, formal or otherwise, of Amaryllidaceae alkaloids reported during the decade 1968 to 1998. Interesting, but as yet unsuccessful synthetic approaches are only referred to when appropriate. The second part lists new alkaloids isolated during the same period, followed by a brief third section dealing with the biological activity associated with some of them. 

Extracts of Amaryllidaceae alkaloids have long been used in traditional medicine for the treatment of a variety of illnesses. As early as the fourth century B.C., Hippocrates had reputedly advised the use of preparations of Amaryllidaceae plants to control uterine tumours [157]. More recently, a systematic bioassay of these alkaloids of different structural types has revealed a diversity of interesting biological properties. Thus, (+)-pretazettine (369) [158,159], and ungeremine (182) [160] show anti-leukemic activity. Cytotoxicity was observed for (-)-lycorine (245) [161], (-)-pseudolycorine (574) [162], 6-a-hydroxycrinamine (575) [163],... 

Figure 8. Biologically active Amaryllidaceae alkaloids (continued next page).

Chapter 3 by S. Prabhakar and M.R. Tavares summarizes recent advances in the synthesis of Amaryllidaceae alkaloids, an important class of naturally-occurring bases and neutral compounds. The increased activity in the synthesis of these alkaloids over the last decade is undoubtedly due to the fact that certain members of this family possess interesting and useful biological properties. Many elegant syntheses, chiral and otherwise, of structures incorporating many asymmetric centres are reviewed. 

This method can be applied to the total synthesis of natural products. The lycorine alkaloids anhydrolycorinone and hippadine have a pyrrolo[3,2,l-de]phenanthridine framework and have been isolated from Amaryllidaceae plants [26]. Hippadine exhibits reversible inhibition of fertility in male rats. Diverse synthetic approaches to the pyrrolophenanthridine alkaloids have been developed because of their potent biological activities [27[. We applied the iron(O)-mediated arylamine cydization described above to a concise synthesis of anhydrolycorinone and hippadine (Scheme 15.7) [28]. 

Members of the family Amaryllidaceae are widely distributed iir the tropics atrd the warm parts of the temperate regions of the world. They are known for their ornamental value and the production of structurally rmique alkaloids, the Amaryllidaceae alkaloids. Some of these alkaloids possess a wide range of biological activities including antitumor, antiviral, antibacterial, antimalarial, central nervous system diseases, immunomodulatory and anti-inflammatory. This chapter emphasizes the bioactivity and bioactive compounds of African Amaryllidaceae. 

Extracts of some amaryllids, as well as alkaloids isolated therefrom, have exhibited various biological activities. These activities cover central nervous system, antitumor, antiviral, antibacterial, anti-inflammatory and antiparasitic conditions 8, 18, 52, 53, 54). However, the more recently demonstrated potent anticancer activity of pancratistatin 14 and the selective, reversible acetylcholinestrase (ACHE) inhibitory activity of galanthamine 5 has fuelled the search for bioactive Amaryllidaceae alkaloids toward the development of antitumor and anti-Alzheimer s drags 55). 

The majority of the active constituents from the family Amaryllidaceae are alkaloids. These alkaloids have been isolated first and thereafter evaluated for their biological activities. A bioassay guided isolation of active extracts may lead to the isolation of interesting non-nitrogenons compounds that could be used as leads for the synthesis of nseful therapentic dmgs. 

R5 = H), respectively. Derivatives of these parent bases have been known since the early 1900s. The benzazepine skeleton has been found to be a component of natural products, e.g., Amaryllidaceae and Papaveraceae alkaloids. Derivatives of the benzazepines have been of interest to medicinal chemists for their wide range of biological activity. 

The crinine alkaloids, which can embody either enantiomeric form of the 2,3, 4,4a-tetrahydro-l//-6//-5,10b-ethanophenanthridine framework, represent an important sub-class within the Amaryllidaceae alkaloid family [53]. Many members of this subclass display interesting biological properties including immuno-stimulatory, cytotoxic and anti-malarial activities. As a consequence, they have been the subject of numerous synthetic studies [53]. 

Plants of the Amaryllidaceae family have been used for thousands of years as herbal remedies. The alkaloids from their extracts have been the object of active chemical investigation for nearly 200 years. Over the past two decades many have been isolated, screened for different biological activities, and synthesized by a number of research groups. An important handicap is the availability of these alkaloids, which are obtained only in minute quantities from natural sources. Since isolation in larger quantities is not praetieal, there is a strong case for the development of syntheses or semisyntheses of these alkaloids and their derivatives as potential prodrugs (35). 

The present review provides coverage of the isolation, spectroscopy, biological activity, and chemical synthesis of the Amaryllidaceae alkaloids present in the genus Narcissus up to July 2005. 

Alkaloids are low-molecular weight, nitrogenous specialized metabolites occuring in approximately 20% of plant species. Many of the about 12,000 structurally elucidated alkaloids show potent biological activity [1, 2]. Particularly, the pharmacological properties of Amaryllidaceae alkaloids (AAs) have been exploited for centuries, and modem medecine... 

Over the past several years, extensive phytochemical and pharmacological analyses have reported the numerous biological activities of Amaryllidaceae alkaloids and numerous AAs... 

Lyeorine was isolated from the bulbs of Lycoris radiata (Amaryllidaceae), and its chemical structure, including the absolute stereochemistry, was reported [3,4]. The biological activities of this alkaloid are similar to those of emetine (Section 1.14), and it was formerly used for the treatment of amoebic dysentery. Gaianthamine was shown to be the same alkaloid as... 

Biological Activity of Colchicine Medicinal Uses of Colchicine Use of Colchicine in Horticulture Amaryllidaceae Alkaloids Biosynthesis Biological Activity... 

Several members of the Amaryllidaceae family of alkaloids display pronounced biological activities, and some Amaryllidaceae plants have played an important role in traditional herbal medicine for the treatment of various ailments. The most prominent examples of Amaryllidaceae alkaloids of biological relevance are narciclasine (55) and its congeners (pancratistatin and 7-deoxypancratistatin) and galantamine (62) (also commonly spelled galanthamine). These natural products also find application in modem medicine, and in this respect, pancratistatin is used in clinical... 

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