Biological evaluation of structurally diverse amaryllidaceae alkaloids and their synthetic derivatives: discovery of novel leads for anticancer drug design.
Twenty-nine Amaryllidaceae alkaloids and their derivatives belonging to the five most common groups, including lycorine, lycorenine, tazettine, crinine, and narciclasine types, were evaluated for antiproliferative, apoptosis-inducing, and anti-invasive 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 anti-invasive properties associated with N-methyllycorine iodide, hippeastrine, clivimine, buphanamine, and narciclasine tetraacetate, all of which were tested at non-toxic concentrations. The anti-invasive activity of buphanamine is particularly promising because this alkaloid is not toxic to cells even at much higher doses. This work has resulted in the identification of several novel leads for anticancer drug design.
Evidente
Antonio
A
Dipartimento di Scienze, del Suolo, della Pianta, dell'Ambiente e delle Produzioni Animali, Università di Napoli Federico II, Portici, Italy. evidente@unina.it
Kireev
Artem S
AS
Jenkins
Aaron R
AR
Romero
Anntherese E
AE
Steelant
Wim F A
WF
Van Slambrouck
Severine
S
Kornienko
Alexander
A
D047151:Amaryllidaceae Alkaloids / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy; D019668:Liliaceae / Q000737:chemistry; D015394:Molecular Structure; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*
D047151:Amaryllidaceae Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts