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.]
| Original language | English |
|---|---|
| Pages (from-to) | 2443-2456 |
| Number of pages | 14 |
| Journal | Chemical Papers |
| Volume | 72 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 1 2018 |
Bibliographical note
Publisher Copyright:© 2018, Institute of Chemistry, Slovak Academy of Sciences.
Funding
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.
| Funders | Funder number |
|---|---|
| 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 | |
| Office of the Assistant Secretary for Health | |
| DOD Prostate Cancer Research Program | P30 CA016056, PCRP W81XWH-16-1-0633, R21 CA205108 |
Keywords
- 6-hydroxyaurones
- Aminomethylation
- Mannich base
- Prostate cancer
ASJC Scopus subject areas
- General Chemistry
- Biochemistry
- General Chemical Engineering
- Industrial and Manufacturing Engineering
- Materials Chemistry
