Flavonoid Constituents of Chorizanthe diffusa with Potential Cancer Chemopreventive Activity

Abstract

An ethyl acetate-soluble extract of Chorizanthe diffusa was found to exhibit significant antioxidant activity, as judged by scavenging stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals and inhibition of 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced free radical formation with cultured HL-60 cells. Bioassay-directed fractionation of this extract using the DPPH antioxidant assay as a monitor led to the isolation of five structurally related flavonoids (1−5), including the novel compound 5,8,3‘,4‘,5‘-pentahydroxy-3,7-dimethoxyflavone (1). Isolates 1−5 demonstrated varying degrees of antioxidant or antimutagenic activity. Two of the compounds, 5,7,3‘,4‘-tetrahydroxy-3-methoxyflavone (2) and quercetin (4), were subsequently found to inhibit carcinogen-induced preneoplastic lesions in a mouse mammary organ culture model. Inhibitory activity of this type is known to correlate with cancer chemopreventive effects in full-term models of tumorigenesis. Keywords: Chorizanthe diffusa; Polygonaceae; flavonoids; 5,8,3‘,4‘,5‘-pentahydroxy-3,7-dimethoxyflavone; antioxidant activity; antimutagenic activity; mouse mammary organ culture; cancer chemoprevention