Efficient synthesis of aurone Mannich bases and evaluation of their antineoplastic activity in PC-3 prostate cancer cells

Antonina V. Popova; Mykhaylo S. Frasinyuk; Svitlana P. Bondarenko; Wen Zhang; Yanqi Xie; Zachary M. Martin; Xianfeng Cai; Michael V. Fiandalo; James L. Mohler; Chunming Liu; David S. Watt; Vitaliy M. Sviripa

doi:10.1007/s11696-018-0485-8

Efficient synthesis of aurone Mannich bases and evaluation of their antineoplastic activity in PC-3 prostate cancer cells

Antonina V. Popova
, Mykhaylo S. Frasinyuk
, Svitlana P. Bondarenko
, Wen Zhang
, Yanqi Xie
, Zachary M. Martin
, Xianfeng Cai
, Michael V. Fiandalo
, James L. Mohler
, Chunming Liu
, David S. Watt
, Vitaliy M. Sviripa

Molecular and Cellular Biochemistry

Producción científica: Article › revisión exhaustiva

14 Citas (Scopus)

Resumen

Abstract: An efficient method for regioselective synthesis of C-7 Mannich bases of 6-hydroxyaurones was accomplished by the N,N-dialkylaminomethylation using aminals prepared from dimethylamine, dipropylamine, bis(2-methoxyethyl)amine, N-methylbutylamine, N-methylbenzylamine, morpholine, piperidine, and 1-methylpiperazine. Further transformation of 7-(N,N-dialkylamino)methyl group in these aurones led to formation of C-7 acetoxymethyl and methoxymethyl derivatives of 6-hydroxyaurones, some of which showed promising inhibition of PC-3 prostate cancer cell proliferation in the high nanomolar to low micromolar range that exceeded that of cisplatin. Graphical abstract: Compound 12c (R³ = Ac, Ar = 3,4-OMePh) displays 75% inhibition of PC-3 prostate cancer cells proliferation at 300 nM concentration.[Figure not available: see fulltext.]

Idioma original	English
Páginas (desde-hasta)	2443-2456
Número de páginas	14
Publicación	Chemical Papers
Volumen	72
N.º	10
DOI	https://doi.org/10.1007/s11696-018-0485-8
Estado	Published - oct 1 2018

Nota bibliográfica

Publisher Copyright:
© 2018, Institute of Chemistry, Slovak Academy of Sciences.

Financiación

Acknowledgments CL and DSW were supported by NCI CA172379. CL and DSW have partial ownership of a new-start company, Epionc, Inc., that seeks to develop these compounds as commercial agents. CL and DSW disclosed this information and complied with requirements to mitigate any potential conflicts of interest in accord with University of Kentucky policy. DSW was also supported by the Office of the Dean of the College of Medicine, by the Center for Pharmaceutical Research and Innovation in the College of Pharmacy, and by NIH Grant Number P30 GM110787 from the National Institute of General Medical Sciences to L. Hersh, PI. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or the NIGMS. DSW was also supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Prostate Cancer Research Program (PCRP) under Award No. W81XWH-16-1-0635. Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense. JLM and MVF were supported by NCI R21 CA205108, PCRP W81XWH-16-1-0633, and NCI P30 CA016056. CL and DSW were supported by NCI CA172379. CL and DSW have partial ownership of a new-start company, Epionc, Inc., that seeks to develop these compounds as commercial agents. CL and DSW disclosed this information and complied with requirements to mitigate any potential conflicts of interest in accord with University of Kentucky policy. DSW was also supported by the Office of the Dean of the College of Medicine, by the Center for Pharmaceutical Research and Innovation in the College of Pharmacy, and by NIH Grant Number P30 GM110787 from the National Institute of General Medical Sciences to L. Hersh, PI. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or the NIGMS. DSW was also supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Prostate Cancer Research Program (PCRP) under Award No. W81XWH-16-1-0635. Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense. JLM and MVF were supported by NCI R21 CA205108, PCRP W81XWH-16-1-0633, and NCI P30 CA016056.

Financiadores	Número del financiador
Center for Pharmaceutical Research and Innovation in the College of Pharmacy
National Institutes of Health (NIH)	P30 GM110787
U.S. Department of Defense	W81XWH-16-1-0635, W81XWH-16-1-0633
National Childhood Cancer Registry – National Cancer Institute	CA205108, CA172379
National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical Sciences
Office of the Assistant Secretary for Health
DOD Prostate Cancer Research Program	P30 CA016056, PCRP W81XWH-16-1-0633, R21 CA205108

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

General Chemistry
Biochemistry
General Chemical Engineering
Industrial and Manufacturing Engineering
Materials Chemistry

Acceder al documento

10.1007/s11696-018-0485-8

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Popova, A. V., Frasinyuk, M. S., Bondarenko, S. P., Zhang, W., Xie, Y., Martin, Z. M., Cai, X., Fiandalo, M. V., Mohler, J. L., Liu, C., Watt, D. S., & Sviripa, V. M. (2018). Efficient synthesis of aurone Mannich bases and evaluation of their antineoplastic activity in PC-3 prostate cancer cells. Chemical Papers, 72(10), 2443-2456. https://doi.org/10.1007/s11696-018-0485-8

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abstract = "Abstract: An efficient method for regioselective synthesis of C-7 Mannich bases of 6-hydroxyaurones was accomplished by the N,N-dialkylaminomethylation using aminals prepared from dimethylamine, dipropylamine, bis(2-methoxyethyl)amine, N-methylbutylamine, N-methylbenzylamine, morpholine, piperidine, and 1-methylpiperazine. Further transformation of 7-(N,N-dialkylamino)methyl group in these aurones led to formation of C-7 acetoxymethyl and methoxymethyl derivatives of 6-hydroxyaurones, some of which showed promising inhibition of PC-3 prostate cancer cell proliferation in the high nanomolar to low micromolar range that exceeded that of cisplatin. Graphical abstract: Compound 12c (R3 = Ac, Ar = 3,4-OMePh) displays 75\% inhibition of PC-3 prostate cancer cells proliferation at 300 nM concentration.[Figure not available: see fulltext.]",

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AU - Zhang, Wen

AU - Xie, Yanqi

AU - Martin, Zachary M.

AU - Cai, Xianfeng

AU - Fiandalo, Michael V.

AU - Mohler, James L.

AU - Liu, Chunming

AU - Watt, David S.

AU - Sviripa, Vitaliy M.

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N2 - Abstract: An efficient method for regioselective synthesis of C-7 Mannich bases of 6-hydroxyaurones was accomplished by the N,N-dialkylaminomethylation using aminals prepared from dimethylamine, dipropylamine, bis(2-methoxyethyl)amine, N-methylbutylamine, N-methylbenzylamine, morpholine, piperidine, and 1-methylpiperazine. Further transformation of 7-(N,N-dialkylamino)methyl group in these aurones led to formation of C-7 acetoxymethyl and methoxymethyl derivatives of 6-hydroxyaurones, some of which showed promising inhibition of PC-3 prostate cancer cell proliferation in the high nanomolar to low micromolar range that exceeded that of cisplatin. Graphical abstract: Compound 12c (R3 = Ac, Ar = 3,4-OMePh) displays 75% inhibition of PC-3 prostate cancer cells proliferation at 300 nM concentration.[Figure not available: see fulltext.]

AB - Abstract: An efficient method for regioselective synthesis of C-7 Mannich bases of 6-hydroxyaurones was accomplished by the N,N-dialkylaminomethylation using aminals prepared from dimethylamine, dipropylamine, bis(2-methoxyethyl)amine, N-methylbutylamine, N-methylbenzylamine, morpholine, piperidine, and 1-methylpiperazine. Further transformation of 7-(N,N-dialkylamino)methyl group in these aurones led to formation of C-7 acetoxymethyl and methoxymethyl derivatives of 6-hydroxyaurones, some of which showed promising inhibition of PC-3 prostate cancer cell proliferation in the high nanomolar to low micromolar range that exceeded that of cisplatin. Graphical abstract: Compound 12c (R3 = Ac, Ar = 3,4-OMePh) displays 75% inhibition of PC-3 prostate cancer cells proliferation at 300 nM concentration.[Figure not available: see fulltext.]

KW - 6-hydroxyaurones

KW - Aminomethylation

KW - Mannich base

KW - Prostate cancer

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Efficient synthesis of aurone Mannich bases and evaluation of their antineoplastic activity in PC-3 prostate cancer cells

Resumen

Nota bibliográfica

Financiación

ODS de las Naciones Unidas

ASJC Scopus subject areas

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