Anticancer evaluation of structurally diverse Amaryllidaceae alkaloids and their synthetic derivatives

Abstract

Plants of the Amaryllidaceae family have been under intense scrutiny for the presence of the specific metabolites responsible for the medicinal properties associated with them. The study began in 1877 with the isolation of alkaloid lycorine from Narcissus pseudonarcissus and since then more than 100 alkaloids, exhibiting diverse biological activities, have been isolated from the Amaryllidaceae plants. Based on the present scientific evidence, it is likely that isocarbostyril constituents of the Amaryllidaceae, such as narciclasine, pancratistatin and their congeners, are the most important metabolites responsible for the therapeutic benefits of these plant species in the folk medical treatment of cancer. Notably, Narcissus poeticus L., used by the ancient Greek physicians, is now known to contain about 0.12 g of narciclasine per kg of fresh bulbs. The focus of the present research work is the chemistry and biology of these compounds as specifically relevant to their potential use in medicine. In particular, the anticancer evaluation of lycorine, narciclasine as well as of other Amaryllidaceae alkaloids and their synthetic derivatives are presented in this paper. The structure-activity relationships among some groups of Amaryllidaceae alkaloids will be discusse

Novel Lycorine Derivatives as Anticancer Agents: Synthesis and In Vitro Biological Evaluation

“…Many factors thus seem involved in the anticancer properties of lycorine and a clear mechanism remains to be determined. Nevertheless, the anticancer properties of lycorine have drawn significant attention from chemists [5,6,[11][12][13]. In the present study we report the synthesis of some novel lycorine derivatives and the evaluation of their in vitro anticancer activities.…”

“…Plant species belonging to the Amaryllidaceae family have been well known for centuries to exhibit diverse medicinal properties. Many of these plants have been used historically for the treatment of cancer, since the oil of the daffodil Narcissus poeticus L. was used by Hippocrates of Kos [5]. The application of narcissus oil in cancer management continued during the middle ages in China, North Africa and Central America [6].…”

Total synthesis of the Amaryllidaceae alkaloid clivonine

“…These alkaloids 15 can mostly be classified as belonging to one of eight skeletally distinct subclasses all derived biosynthetically from a common precursor, norbelladine. [1][2][3] Clivonine (1), along with homolycorine (2), hippeastrine (3) and lycorenine (4) are prominent members of the lycorenine subclass; these alkaloids 20 feature a tetracyclic 2-benzopyrano-[3,4-g]indole skeleton and display growth inhibition of various tumour cells, [4][5][6] DNA binding properties, 7 anti-viral activity, 8,9 antifungal activity, 10 and insect antifeedant activity 11 ( Figure 1). 12 (+)-Clivonine (1) was first isolated as white prisms in 25 0.0007% yield from an ethanolic extract of freshly collected rhizomes and leaves of Clivia miniata Regel in 1956 by Wildman, who also tentatively proposed the correct gross topology of the molecule.…”

The study of chemical composition and pharmacological action of the alkaloid from plants of Lycoris Herb

“…It isolated 14 Galanthamine alkaloids from Lycoris herb(figure 2), Galanthamine (18) isolated from L.haywardii [15] ; Galanthamine N-oxide(19) isolated from L.incanata [11] ; lycoramine (20) and Lycoramine N-oxide (21)and Sanguinine N-oxide (24) isolated from L.haywardii [4] ; O-demethyllycoramine (22) isolated from L.aurea [16] ; Sangiiinine(23) isolated from L.sanguinea [12] ; epi-galanthamine(25) isolated from L.squamigera [8] ; Narwedine(26), Norgalanthamine (27) and N-allylnorgalanthamine(28) isolated from L.guangxiensis [10] ; N-demethyllycoramine (29) isolated from L.haywardii [15] ; Norsanguinine (30) and norbutsanguininem(31) isolated from L.sanguinea [27] .…”

“…Galantamine the performance of AchE inhibition is competitive reversible inhibition, the role of the IC50 is 1.9 μmol/L [27] ; 1-O-acetyllycorine of Lycorine type alkaloids has significant inhibitory activity and its intensity is equal to 2 times of Galanthamine, Lycorine of Lycoris type alkaloids, 1,2 diacetyl Lycorine anti-AchE activity is poor [28] ; In addition, the study also found that montanine of AchE showed some inhibition, the strength of galanthamine was slightly lower [29] . Narciprimine and 6-Hydroxycrinamine also has anti-AchE activity [30] .…”