Title
Antiproliferative Alkaloids from Alangium longiflorum, an Endangered Tropical Plant Species
Author
Misa Takeuchi, Yohei Saito, Masuo Goto, Katsunori Miyake, David J. Newman, Barry R. O’Keefe, Kuo-Hsiung Lee, Kyoko Nakagawa-Goto
Year
2018
Journal
Journal of Natural Products
Abstract
Alangium longiflorum is currently in extinction crisis, which will likely severely hamper further phytochemical investigation of this plant species from new collections. A crude extract of leaves of A. longiflorum (N33539), collected for the U.S. National Cancer Institute in 1989, showed potent cancer cell line antiproliferative activity. A phytochemical study resulted in the isolation of 17 secondary metabolites, including two new tetrahydroisoquinoline alkaloids, 8-hydroxytubulosine (1) and 2′-O-trans-sinapoylisoalangiside (2), as well as a new sinapolyloxylupene derivative (3). Using in-house assays and NCI-60 panel screening, compound 1 displayed broad-spectrum inhibitory activity at submicromolar levels against most tested tumor cell lines, except for drug-transporter-overexpressing cells. Compound 1 caused accumulation of sub-G1 cells with no effect on cell cycle progression, suggesting that this substance is an apoptosis inducer.
Instrument
J-820
Keywords
Circular dichroism, Absolute configuration, Cotton effect, Natural products, Pharmaceutical