
pmid: 40516169
The plant family Amaryllidaceae is embellished with a diverse array of antiproliferative alkaloid principles. Chief amongst these are the lycorine alkaloids, which have attracted considerable attention as potential anticancer drugs. This account tracks developments in the field with these substances encompassing the years 2015-2019. Twenty-nine compounds were screened against nearly eighty cancer cell lines representing seventeen different types of cancer. Submicromolar level activities were recorded against leukemia, myeloma and breast cancer cells. The response of lycorine (IC50 0.6 μM) to HL-60 myeloid leukemia cells was particularly striking. Promising activities were also documented from in vivo models of brain, lung, colon, prostate and breast cancer cells (in the 5-10 mg/kg/day dosage range). The screenings indicated these compounds to be efficacious without attendant detrimental effects towards control animals. Structure-activity relationship studies afforded useful insight to the elements of the anticancer pharmacophore, such as the necessity for the A-ring methylenedioxy and C-ring hydroxy functionalities. The mechanisms of action were intensively examined, with over twenty individual areas identified wherein such probes have been made. Of prominence here was the apoptosis-inducing abilities of lycorine against (amongst others) leukemia, pancreatic, bladder, liver and bone cancer cells, involving the modulation of key mediators such as caspase-3, p53, PARP, Bax and Bcl-2. Useful insights also emerged from docking studies undertaken with various cancer-related proteins, such as VEGF, HDAC, PI3Kα, c-Met kinase and EGFR. The lycorine alkaloids have proved to be highly versatile entities, readily embracing multiple facets of anticancer drug discovery.
Dose-Response Relationship, Drug, Molecular Structure, Caspase 3, Amaryllidaceae, Apoptosis, Antineoplastic Agents, Phytogenic, Phenanthridines, Structure-Activity Relationship, Alkaloids, Cell Line, Tumor, Amaryllidaceae Alkaloids, Animals, Humans, Drug Screening Assays, Antitumor, Cell Proliferation
Dose-Response Relationship, Drug, Molecular Structure, Caspase 3, Amaryllidaceae, Apoptosis, Antineoplastic Agents, Phytogenic, Phenanthridines, Structure-Activity Relationship, Alkaloids, Cell Line, Tumor, Amaryllidaceae Alkaloids, Animals, Humans, Drug Screening Assays, Antitumor, Cell Proliferation
| selected citations These citations are derived from selected sources. This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | 2 | |
| popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network. | Average | |
| influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | Average | |
| impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network. | Average |
