Efficient synthesis of aurone Mannich bases and evaluation of their antineoplastic activity in PC-3 prostate cancer cells
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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.
Keywords6-hydroxyaurones Mannich base Aminomethylation Prostate cancer
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.
- Lipeeva, A. V.; Shul’ts, E. E.; Shakirov, M. M.; Bagryanskaya, I. Y.; Tolstikov, G. A. Russ. J. Org. Chem. 2013, 49, 403-411Google Scholar