Antimutagenic constituents of Casimiroa edulis with potential cancer chemopreventive activity

An ethyl acetate extract derived from the seeds of the medicinal and food plant Casimiroa edulis inhibited mutagenicity induced by 7,12-dimethylbenz[a]anthracene (DMBA) with Salmonella typhimurium strain TM677. It also showed complete inhibition of DMBA-induced preneoplastic lesions with an in vitro mouse mammary gland organ culture system at a concentration of 10 mu g/mL. Bioassay-guided phytochemical investigation of this extract using antimutagenicity as a monitor led to the isolation of four furocoumarins, constituted by the known compounds phellopterin (1) and isopimpinellin (2) and the novel compounds (R,S)-5-methoxy-8-[(6,7-dihydroxy-3,7-dimethyl-2-octenyl)oxy]psoralen (3) and (R,S)-8-[(6,7-dihydroxy-3,7-dimethyl-2-octenyl)oxy]psoralen (4). Four known alkaloids, casimiroin (5), 4-methoxy-1-methyl-2(1H)-quinolinone (6), 5-hydroxy-1-methyl-2-phenyl-4-quinolone (7), and gamma-fagarine (8), and two known flavonoids, zapotin (9) and 5,6,2'-trimethoxyflavone (10), were also isolated. Of these isolates, compounds 3 and 5 showed the most potent antimutagenic effects in the forward mutagen assay utilizing S. typhimurium strain TM677, whereas casimiroin (5) and 5,6,2'-trimethoxyflavone (10) significantly inhibited the formation of DMBA-induced preneoplastic lesions in mouse mammary gland organ culture.