Cytotoxic lycorine alkaloids of the plant family Amaryllidaceae.

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.