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Chemical Papers

, Volume 72, Issue 10, pp 2443–2456 | Cite as

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
Original Paper

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.

Keywords

6-hydroxyaurones Mannich base Aminomethylation Prostate cancer 

Notes

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.

Supplementary material

11696_2018_485_MOESM1_ESM.pdf (18.5 mb)
Supplementary material 1 (PDF 18,965 KB)
11696_2018_485_MOESM2_ESM.xlsx (18 kb)
Supplementary material 1 (XLSX 18 KB)

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Copyright information

© Institute of Chemistry, Slovak Academy of Sciences 2018

Authors and Affiliations

  • Antonina V. Popova
    • 1
  • Mykhaylo S. Frasinyuk
    • 1
    • 2
    • 3
  • Svitlana P. Bondarenko
    • 4
  • Wen Zhang
    • 2
    • 5
  • Yanqi Xie
    • 2
    • 3
  • Zachary M. Martin
    • 2
    • 3
  • Xianfeng Cai
    • 2
    • 5
  • Michael V. Fiandalo
    • 6
  • James L. Mohler
    • 6
  • Chunming Liu
    • 2
    • 5
  • David S. Watt
    • 2
    • 3
    • 5
  • Vitaliy M. Sviripa
    • 3
    • 7
  1. 1.Institute of Bioorganic and PetrochemistryNational Academy of Science of UkraineKyivUkraine
  2. 2.Department of Molecular and Cellular Biochemistry, College of MedicineUniversity of KentuckyLexingtonUSA
  3. 3.Center for Pharmaceutical Research and Innovation, College of PharmacyUniversity of KentuckyLexingtonUSA
  4. 4.National University of Food TechnologiesKyivUkraine
  5. 5.Lucille Parker Markey Cancer CenterUniversity of KentuckyLexingtonUSA
  6. 6.Department of UrologyElm & Carlton Streets, Roswell Park Comprehensive Cancer CenterBuffaloUSA
  7. 7.Department of Pharmaceutical Sciences, College of PharmacyUniversity of KentuckyLexingtonUSA

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