Biological Evaluation of Structurally Diverse Amaryllidaceae Alkaloids and their Synthetic Derivatives: Discovery of Novel Leads for Anticancer Drug Design

Abstract

Twenty nine Amaryllidaceae alkaloids and their derivatives belonging to five most common groups, including lycorine-, lycorenine-, tazettine-, crinine-, and narciclasine-types, were evaluated for antiproliferative, apoptosis inducing and antiinvasive activities in vitro. The antiproliferative properties of each test compound are in agreement with those reported in the literature, while the high potency of amarbellisine is reported for the first time. It was also found that with the exception of ungeremine, amarbellisine and hippeastrine, the antiproliferative effect of the potent compounds is apoptosis-mediated. Thus, apoptosis in Jurkat cells was triggered by narciclasine, narciclasine tetraacetate, C10b-R-hydroxypancratistatin, cis-dihydronarciclasine, trans-dihydronarciclasine, lycorine, 1-O-acetyllycorine, lycorine-2-one, pseudolycorine, and haemanthamine. With the exception of narciclasine, lycorine and haemanthamine, the apoptosis inducing properties of these compounds are reported for the first time. The collagen type I invasion assay revealed potent antiinvasive properties associated with N-methyllycorine iodide, hippeastrine, clivimine, buphanamine, and narciclasine tetraacetate, all of which were tested at non-toxic concentrations. The antiinvasive activity of buphanamine is particularly promising since this alkaloid is not toxic to cells even at much higher doses. This work has resulted in identification of several novel leads for anticancer drug design.

Anticancer evaluation of structurally diverse Amaryllidaceae alkaloids and their synthetic derivatives

“…This derivative may also be a prodrug of 1 and its somewhat weaker apoptosis inducing potential in Jurkat cells (Fig. 8) may be explained by the 24 h treatment, which may be insufficient for the complete hydrolytic removal of the acetate ester (Evidente et al 2009). …”

“…The collagen invasion assay revealed potent antiinvasive properties associated with N-methyllycorine iodide (6), hippeastrine (13), clivimine (17), buphanamine (23), and narciclasine tetraacetate (26), all of which were tested at non-toxic concentrations. These results could represent a starting point to carry out a structure-activity relationship study of alkaloids, synthetic derivatives and natural analogues for each ring-type group with the aim to find compounds with significantly increased antiinvasive activity (Evidente et al 2009). …”

“…This work has resulted in identification of several novel leads for anticancer drug design (Evidente et al 2009). Derivatives 2, 3, 4, 5, 6 and 7 (Fig.…”

Structural basis for the inhibition of the eukaryotic ribosome

“…Homoharringtonine is a marketed drug for the treatment of chronic myeloid leukaemia 37 . Lycorine and narciclasine are alkaloids known for their medicinal and toxic properties 38 . T-2 toxin, deoxynivalenol and verrucarin A are widespread mycotoxins representatives of the three major trichothecenes subclasses 39 .…”

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

“…The study found that Galanthamine and O-desmethyl galantamine from Galanthamine type alkaloids have anti-acetylcholinesterase(AchE) activity. 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] .…”