Cytotoxic Constituents of Cryptocarya rubra Investigated Using an Extract Housed in a Repository

The genus Cryptocarya belongs to the pantropical family Lauraceae, of which several species grow in Pacific Rim tropical rainforests. Previous studies have shown that cryptocaryone is the main cytotoxic compound of species of this genus, but a detailed phytochemical investigation about Cryptocarya rubra has not been reported. As an extension of a search for new natural product anticancer agents from diverse organisms, a small-scale sample of a dichloromethane partition of a methanol-soluble extract of C. rubra, collected in Hawaii, was found to be cytotoxic toward the HT-29 human colon cancer cell line and was selected as a lead. This extract repository was donated to IHVR by Merck Research Laboratories, Rahway, NJ. Using column chromatography guided by cytotoxicity to HT-29 cells, cryptocaryone and several new and known analogues, including cryptocaryanones A and B and bicaryanone A, were isolated. The structures of all isolates were established from their IR, UV, NMR, and mass spectra, and their absolute configurations were determined by analysis of their CD spectra and supported by the relative configuration determination of cryptocaryanones A and B using single-crystal X-ray diffraction. All isolates have been evaluated for their cytotoxicity against HT-29 cells, and several compounds were found to be active, with cryptocaryone (IC₅₀, 0.32µM) being the most potently cytotoxic compound.