Chemical constituents of Lycoris albiflora and their cytotoxic activities.

An alcoholic extract of Lycoris albiflora (Amaryllidaceae) showed potent cytotoxic activity against HL-60 cells with an IC50 value of 1.7 microg/mL. Phytochemical examination of the extract resulted in the isolation of 15 alkaloids, including two phenanthridine-type alkaloids (1, 2), one benzylphenethylamine-type alkaloid (3), two crinane-type alkaloids (4, 5), one pyrrolophenanthridine-type alkaloid (6), six lycorenan-type alkaloids (7-12), and three galanthamine-type alkaloids (13-15), together with three neolignans (16-18), two flavans (19, 20), and two acetophenone derivatives (21, 22). Compound 3 (hostasinine A) has not been isolated from Amaryllidaceae plants, and 1, 2, 4, 5, 7-9, 11, 12 and 14-22 are the first isolation and identification from L. albiflora. The phenanthridine-type alkaloids (1, 2), as well as the alkaloids (3-5), exhibited potent cytotoxic activities against not only HL-60 cells but also HSC-2 cells, thus leading to the conclusion that these alkaloids are mainly responsible for the cytotoxicity of the L. albiflora extract. Compound 1 (lycoricidinol), with the most potent cytotoxic activities, induced apoptosis in both HL-60 cells and HSC-2 cells. It is notable that 1 induced transient autophagy and morphological changes in mitochondria in the early stages of the apoptotic cell death process in HSC-2 cells.