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

doi:10.1002/cmdc.201600008

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

Molecular and Cellular Biochemistry

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

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 language	English
Pages (from-to)	600-611
Number of pages	12
Journal	ChemMedChem
Volume	11
Issue number	6
DOIs	https://doi.org/10.1002/cmdc.201600008
State	Published - Mar 17 2016

Bibliographical note

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

Keywords

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
General Pharmacology, Toxicology and Pharmaceutics
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/cmdc.201600008

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@article{1671f806488e4a83ba5a1de09c9cd2bf,

title = "Antineoplastic Isoflavonoids Derived from Intermediate ortho-Quinone Methides Generated from Mannich Bases",

abstract = "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.",

keywords = "Mannich reactions, inverse electron-demand Diels-Alder reaction, isoflavonoids, ortho-quinone methides, prostate cancer PC-3 cell line",

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

note = "Publisher Copyright: {\textcopyright} 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.",

year = "2016",

month = mar,

day = "17",

doi = "10.1002/cmdc.201600008",

language = "English",

volume = "11",

pages = "600--611",

number = "6",

}

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T1 - Antineoplastic Isoflavonoids Derived from Intermediate ortho-Quinone Methides Generated from Mannich Bases

AU - Frasinyuk, Mykhaylo S.

AU - Mrug, Galyna P.

AU - Bondarenko, Svitlana P.

AU - Khilya, Volodymyr P.

AU - Sviripa, Vitaliy M.

AU - Syrotchuk, Oleksandr A.

AU - Zhang, Wen

AU - Cai, Xianfeng

AU - Fiandalo, Michael V.

AU - Mohler, James L.

AU - Liu, Chunming

AU - Watt, David S.

PY - 2016/3/17

Y1 - 2016/3/17

N2 - 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.

AB - 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.

KW - Mannich reactions

KW - inverse electron-demand Diels-Alder reaction

KW - isoflavonoids

KW - ortho-quinone methides

KW - prostate cancer PC-3 cell line

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UR - http://www.scopus.com/inward/citedby.url?scp=84959875663&partnerID=8YFLogxK

U2 - 10.1002/cmdc.201600008

DO - 10.1002/cmdc.201600008

M3 - Article

C2 - 26889756

AN - SCOPUS:84959875663

SN - 1860-7179

VL - 11

SP - 600

EP - 611

JO - ChemMedChem

JF - ChemMedChem

IS - 6

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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