Cytotoxicity Studies of Lycorine Alkaloids of the Amaryllidaceae

Abstract

The plant family Amaryllidaceae is renowned for its unique alkaloid constituents which possess a significant array of structural diversity. Several of these alkaloids are known for their interesting biological properties, of which galanthamine and pancratistatin have acquired a privileged status due to their relevance in the pharmaceutical arena. In particular, galanthamine represents the first prescription drug emanating from the Amaryllidaceae after its approval by the FDA in 2001 for the treatment of Alzheimer's disease. Following on this commercial success there have been sustained projections for the emergence of an anticancer agent related to pancratistatin due to the potency, selectivity, low toxicity and high tolerability typifying targets of this series of alkaloids. The lycorine series of alkaloids have also garnered widespread interest as cytotoxic agents and were amongst the earliest of the Amaryllidaceae constituents to exhibit such activity. To date over 100 of such naturally-occurring or synthetically-derived alkaloids have been screened for cytotoxic effects against a number of cancer cell lines. This survey examines the cytotoxic properties of lycorine alkaloids, highlights the outcomes of structure-activity relationship orientated studies and affords plausible insights to the mechanistic rationale behind these effects.

Lycorine: A prospective natural lead for anticancer drug discovery

“…2B]. The structural parameters that provide a significant contribution to its activity include the presence of planarity of the molecule, olefin or dioxole ring, the function of hydroxyl groups and the presence of a positive charge on the nitrogen and the amine group [9,23,24].…”

The Genus Nerine Herb. (Amaryllidaceae): Ethnobotany, Phytochemistry, and Biological Activity

“…Lycorine (44) appeared to be the strongest anticancer compound in a single-digit micromolar range and showed a cytostatic rather than cytotoxic effect. Lycorine displays significant in vitro cytotoxic activity against several different types of cancer cell lines, including Rauscher, HeLa, P-388, U-373, HepG2, 3T3, KB, Molt-4, HT-1080, COL-2, and ZR-75-1 [69]. Furthermore, lycorine (44) displayed significant therapeutic benefit at nontoxic doses in mice bearing grafts of the B16F10 melanoma model.…”

Antifungal constituents of the plant family Amaryllidaceae

“…By far the largest alkaloid group of the Amaryllidaceae, lycorane alkaloids are typified by a pyrrolo‐phenanthridine skeleton forged by the ethyl tether adjoining the nitrogen and C‐4 atoms (Jin, ). They are known for a wide range of biological properties (Bastida et al, ) but mainly for their antiproliferative activities (Nair & Van Staden, ). Seven representatives of the lycorane group were identified in studies of fungal pathogenesis, including lycorine ( 5 ), amarbellisine ( 6 ), galanthine ( 7 ), 9‐ O ‐demethylgalanthine ( 8 ), caranine ( 9 ), acetylcaranine ( 10 ), and pseudolycorine ( 11 ) (Scheme ).…”

“…Plants of the family are also popular in traditional medicine where they are used to treat a wide variety of ailments (Hutchings, Scott, Lewis, & Cunningham, ; Nair, Bastida, Codina, Viladomat, & Van Staden, ; Nair & Van Staden, ; Nair, Van Staden, Bonnet, & Wilhelm, , ; Viladomat, Bastida, Codina, Nair, & Campbell, ; Watt & Breyer‐Brandwijk, ). The knowledge assimilated from such practices has led to significant discoveries being made in the pharmaceutical arena, especially in relation to cancer and motor‐neuron disease therapies (Heinrich, ; Heinrich & Teoh, ; Kornienko & Evidente, ; Nair, Bastida, Viladomat, & Van Staden, ; Nair & Van Staden, ; Nair, Van Staden, & Bastida, ). These successes are attributable to the isoquinoline alkaloid constituents of the Amaryllidaceae, a distinguishing chemotypic feature of the family, which are responsible for most of its biological properties (Bastida, Lavilla, & Viladomat, ; Berkov, Codina, & Bastida, ; De Andrade et al, ; Jin, ; Nair et al, ; Viladomat et al, ).…”