Synthesis of novel 4-Boc-piperidone chalcones and evaluation of their cytotoxic activity against highly-metastatic cancer cells.

Autor: Ocasio-Malavé C; Faculty of Science and Technology, Department of Natural Sciences, Inter American University of Puerto Rico, Metropolitan Campus, PO Box 191293, San Juan, PR 00919, USA., Donate MJ; School of Pharmacy, Department of Pharmaceutical Sciences, University of Puerto Rico, Medical Sciences Campus, PO Box 365067, San Juan, PR 00936, USA; University of Puerto Rico Comprehensive Cancer Center, PO Box 363027, San Juan, PR 00936, USA., Sánchez MM; University of Puerto Rico Comprehensive Cancer Center, PO Box 363027, San Juan, PR 00936, USA., Sosa-Rivera JM; School of Pharmacy, Department of Pharmaceutical Sciences, University of Puerto Rico, Medical Sciences Campus, PO Box 365067, San Juan, PR 00936, USA; University of Puerto Rico Comprehensive Cancer Center, PO Box 363027, San Juan, PR 00936, USA., Mooney JW; Faculty of Science and Technology, Department of Natural Sciences, Inter American University of Puerto Rico, Metropolitan Campus, PO Box 191293, San Juan, PR 00919, USA., Pereles-De León TA; Faculty of Science and Technology, Department of Natural Sciences, Inter American University of Puerto Rico, Metropolitan Campus, PO Box 191293, San Juan, PR 00919, USA., Carballeira NM; Department of Chemistry, University of Puerto Rico, Rio Piedras Campus, 17 Ave Universidad STE 1701, San Juan, PR 00925, USA., Zayas B; School of Science, Technology & Environment, Universidad Ana G. Méndez, Cupey Campus, PO Box 21150, San Juan, PR 00928, USA., Vélez-Gerena CE; School of Science, Technology & Environment, Universidad Ana G. Méndez, Cupey Campus, PO Box 21150, San Juan, PR 00928, USA., Martínez-Ferrer M; School of Pharmacy, Department of Pharmaceutical Sciences, University of Puerto Rico, Medical Sciences Campus, PO Box 365067, San Juan, PR 00936, USA; University of Puerto Rico Comprehensive Cancer Center, PO Box 363027, San Juan, PR 00936, USA., Sanabria-Ríos DJ; Faculty of Science and Technology, Department of Natural Sciences, Inter American University of Puerto Rico, Metropolitan Campus, PO Box 191293, San Juan, PR 00919, USA. Electronic address: dsanabria@intermetro.edu.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2020 Jan 01; Vol. 30 (1), pp. 126760. Date of Electronic Publication: 2019 Oct 28.
DOI: 10.1016/j.bmcl.2019.126760
Abstrakt: In this study, six curcuminoids containing a tert-butoxycarbonyl (Boc) piperidone core were successfully synthesized, five of them are novel compounds reported here for the first time. These compounds were prepared through an aldolic condensation by adding tetrahydropyranyl-protected benzaldehydes or substituted benzaldehyde to a reaction mixture containing 4-Boc-piperidone and lithium hydroxide in an alcoholic solvent. A 44-94% yield was obtained supporting the developed methodology as a good strategy for the synthesis of 4-Boc-piperidone chalcones. Cytotoxic activity against LoVo and COLO 205 human colorectal cell lines was observed at GI 50 values that range from 0.84 to 34.7 μg/mL, while in PC3 and 22RV1 human prostate cancer cell lines, GI 50 values ranging from 17.1 to 22.9 μg/mL were obtained. Results from biochemical assays suggest that the cytotoxicity of the 4-Boc-piperidone chalcones can be linked to their ability to induce apoptosis, decrease the activity of NFκB and cellular proliferation. Our findings strongly support the potential of Boc-piperidone chalcones as novel cytotoxic agents against highly-metastatic cancer cells.
(Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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