Isoflavones with unusually modified B-rings and their evaluation as antiproliferative agents

Six novel isoflavone derivatives along with four known isoflavones were isolated from a culture of a highly nickel-resistant strain of Streptomyces mirabilis from a former uranium mining area. The structures of 7-hydroxy-3',5'-dihydroxyisoflavone (5), 5,7-dihydroxy-3',5'-dihydroxyisoflavone (6), 2'-hydroxy-3'-methoxygenistein (7), as well as hydroisoflavones A-C (8-10) were elucidated by MS and NMR analyses. Compounds 8-10 feature yet unprecedented types of non-aromatic, hydroxylated B rings, which result from plant isoflavone biotransformation. All new compounds display weak cytotoxic but potent antiproliferative activities. The anti-oestrogenic properties of 8 against MCF-7 human breast cancer cell line (GI(50): 6 microM) is even higher than the reference compound genistein.