Antineoplastic Isoflavonoids Derived from Intermediate ortho-Quinone Methides Generated from Mannich Bases

Mykhaylo S. Frasinyuk, Galyna P. Mrug, Svitlana P. Bondarenko, Volodymyr P. Khilya, Vitaliy M. Sviripa, Oleksandr A. Syrotchuk, Wen Zhang, Xianfeng Cai, Michael V. Fiandalo, James L. Mohler, Chunming Liu, David S. Watt

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


The regioselective condensations of various 7-hydroxyisoflavonoids with bis(N,N-dimethylamino)methane in a Mannich reaction provided C-8 N,N-dimethylaminomethyl-substituted isoflavonoids in good yield. Similar condensations of 7-hydroxy-8-methylisoflavonoids led to the C-6-substituted analogs. Thermal eliminations of dimethylamine from these C-6 or C-8 N,N-dimethylaminomethyl-substituted isoflavonoids generated ortho-quinone methide intermediates within isoflavonoid frameworks for the first time. Despite other potential competing outcomes, these ortho-quinone methide intermediates trapped dienophiles including 2,3-dihydrofuran, 3,4-dihydro-2H-pyran, 3-(N,N-dimethylamino)-5,5-dimethyl-2-cyclohexen-1-one, 1-morpholinocyclopentene, and 1-morpholinocyclohexene to give various inverse electron-demand Diels-Alder adducts. Several adducts derived from 8-N,N-dimethylaminomethyl-substituted isoflavonoids displayed good activity in the 1-10 μm concentration range in an in vitro proliferation assay using the PC-3 prostate cancer cell line.

Original languageEnglish
Pages (from-to)600-611
Number of pages12
Issue number6
StatePublished - Mar 17 2016

Bibliographical note

Publisher Copyright:
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.


  • Mannich reactions
  • inverse electron-demand Diels-Alder reaction
  • isoflavonoids
  • ortho-quinone methides
  • prostate cancer PC-3 cell line

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology, Toxicology and Pharmaceutics (all)
  • Organic Chemistry


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