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.
Ndejouong
B Le S Tchize
Ble S
Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstr. 11a, 07745 Jena, Germany.
Sattler
I
I
Dahse
H-M
HM
Kothe
E
E
Hertweck
C
C
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D000975:Antioxidants / Q000032:analysis / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001711:Biotransformation; D018938:Caco-2 Cells / Q000473:pathology; D002273:Carcinogens / Q000494:pharmacology; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D019833:Genistein / Q000032:analysis / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D007529:Isoflavones / Q000737:chemistry / Q000627:therapeutic use*; D008958:Models, Molecular; D018384:Oxidative Stress / Q000187:drug effects; D024301:Plant Bark / Q000737:chemistry
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; D002273:Carcinogens; D007529:Isoflavones; D019833:Genistein