Cytotoxic Agents in the Minor Alkaloid Groups of the Amaryllidaceae

Abstract

Over 600 alkaloids have to date been identified in the plant family Amaryllidaceae. These have been arranged into as many as 15 different groups based on their characteristic structural features. The vast majority of studies on the biological properties of Amaryllidaceae alkaloids have probed their anticancer potential. While most efforts have focused on the major alkaloid groups, the volume and diversity afforded by the minor alkaloid groups have promoted their usefulness as targets for cancer cell line screening purposes. This survey is an in-depth review of such activities described for around 90 representatives from 10 minor alkaloid groups of the Amaryllidaceae. These have been evaluated against over 60 cell lines categorized into 18 different types of cancer. The montanine and cripowellin groups were identified as the most potent, with some in the latter demonstrating low nanomolar level antiproliferative activities. Despite their challenging molecular architectures, the minor alkaloid groups have allowed for facile adjustments to be made to their structures, thereby altering the size, geometry, and electronics of the targets available for structure-activity relationship studies. Nevertheless, it was seen with a regular frequency that the parent alkaloids were better cytotoxic agents than the corresponding semisynthetic derivatives. There has also been significant interest in how the minor alkaloid groups manifest their effects in cancer cells. Among the various targets and pathways in which they were seen to mediate, their ability to induce apoptosis in cancer cells is most appealing.

Antitumor evaluation of amaryllidaceae alkaloids on cancer cell lines: A literature review

“…The results also highlight the potential synergistic effects of amaryllidaceae alkaloids with standard chemotherapeutic agents. Combination therapy with alkaloids has shown promise in enhancing the cytotoxic effects of conventional drugs, making them potential adjuvants for cancer treatment [25,26,35]. However, despite the promising findings, some studies revealed the emergence of drug resistance mechanisms in response to amaryllidaceae alkaloid treatment.…”

Inhibition of the Eukaryotic 80S Ribosome as a Potential Anticancer Therapy: A Structural Perspective

“…In the same work the X-ray structures of two Amaryllidaceae alkaloids (AAs), lycorine (LYC) and narciclasine (NAR), were disclosed. AAs are natural compounds that can be extracted from Amaryllidaceae bulbs, which share a common chemical architecture and have been shown to inhibit cancer cell growth by halting protein synthesis [24,29,49,54]. A remarkable finding is the position of the dioxole moiety with regard to the A-site cleft.…”

Amaryllidaceae Alkaloids Decrease the Proliferation, Invasion, and Secretion of Clinically Relevant Cytokines by Cultured Human Colon Cancer Cells

“…460–370), who treated uterine tumors with a pessary prepared from narcissus oil [ 15 ]. To date, more than 600 alkaloids of 15 chemical groups exhibiting various biological activities have been isolated from the Amaryllidaceae plants [ 16 ]. Most of these alkaloids belong to the lycorane and crinane chemical groups; however, the majority of the scientists investigating these plants as a source of anticancer agents share the opinion that the isocarbostyril non-basic constituents of the Amaryllidaceae, such as narciclasine (NAR) and pancrastitatin (PANC) ( Figure 1 ), are likely to be the most important plant metabolites responsible for the anticancer properties of these plant species in folk medicine.…”

“…Most of these alkaloids belong to the lycorane and crinane chemical groups; however, the majority of the scientists investigating these plants as a source of anticancer agents share the opinion that the isocarbostyril non-basic constituents of the Amaryllidaceae, such as narciclasine (NAR) and pancrastitatin (PANC) ( Figure 1 ), are likely to be the most important plant metabolites responsible for the anticancer properties of these plant species in folk medicine. Indeed, isocarbostyrils NAR and PANC are nanomolar antiproliferative agents in cancer cell cultures [ 16 ]. Notably, Narcissus poeticus L., used by Hippocrates, is now known to contain some 0.12 g of NAR per kg of fresh bulbs [ 17 ].…”