title: Application of Mannich bases to the synthesis of hydroxymethylated isoflavonoids as potential antineoplastic agents.
abstract: The regiospecific Mannich aminomethylation of 7-hydroxyisoflavonoids using bis(N,N-dimethylamino)methane afforded C-8 substituted N,N-dimethylaminomethyl adducts, and the regioselective aminomethylation of 5-hydroxy-7-methoxyisoflavonoids afforded predominantly the C-6 substituted N,N-dimethylaminomethyl adducts. Acetylation of these C-6 or C-8 Mannich bases with potassium acetate in acetic anhydride provided access to the corresponding acetoxymethyl derivatives that were subsequently converted to hydroxymethyl- and methoxymethyl-substituted 5-hydroxy- or 7-hydroxyisoflavonoids related to naturally occurring flavonoids. The C-8 acetoxymethyl, hydroxymethyl or methoxymethyl-substituted isoflavonoids possessed promising inhibitory potency in the low micromolar range in a prostate cancer PC-3 cell proliferation assay.
authors.affiliation: Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Science of Ukraine, Kyiv 02094, Ukraine.
authors.forename: Mykhaylo S
authors.initials: MS
authors.lastname: Frasinyuk
authors.forename: Galyna P
authors.initials: GP
authors.lastname: Mrug
authors.forename: Svitlana P
authors.initials: SP
authors.lastname: Bondarenko
authors.forename: Vitaliy M
authors.initials: VM
authors.lastname: Sviripa
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Cai
authors.forename: Michael V
authors.initials: MV
authors.lastname: Fiandalo
authors.forename: James L
authors.initials: JL
authors.lastname: Mohler
authors.forename: Chunming
authors.initials: C
authors.lastname: Liu
authors.forename: David S
authors.initials: DS
authors.lastname: Watt
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D006900:Hydroxylation; D007529:Isoflavones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008352:Mannich Bases / Q000138:chemical synthesis / Q000737:chemistry*; D008745:Methylation; D011467:Prostate / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D007529:Isoflavones; D008352:Mannich Bases