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

  • Bioorg Med Chem Lett. 2020 Jan 1;30(1):126760. doi: 10.1016/j.bmcl.2019.126760.
Carlimar Ocasio-Malavé  1 ,  Metsiel J Donate  2 ,  María M Sánchez  3 ,  Jesús M Sosa-Rivera  2 ,  Joseph W Mooney  1 ,  Tomás A Pereles-De León  1 ,  Néstor M Carballeira  4 ,  Beatriz Zayas  5 ,  Christian E Vélez-Gerena  5 ,  Magaly Martínez-Ferrer  2 ,  David J Sanabria-Ríos  6
Affiliations
  • 1. 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.
  • 2. 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.
  • 3. University of Puerto Rico Comprehensive Cancer Center, PO Box 363027, San Juan, PR 00936, USA.
  • 4. Department of Chemistry, University of Puerto Rico, Rio Piedras Campus, 17 Ave Universidad STE 1701, San Juan, PR 00925, USA.
  • 5. School of Science, Technology & Environment, Universidad Ana G. Méndez, Cupey Campus, PO Box 21150, San Juan, PR 00928, USA.
  • 6. 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: [email protected].
PMID: 31767266 DOI: 10.1016/j.bmcl.2019.126760
Abstract

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 GI50 values that range from 0.84 to 34.7 μg/mL, while in PC3 and 22RV1 human prostate Cancer cell lines, GI50 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.

Keywords
Apoptosis; Cancer; Cell proliferation; Curcumin; Curcumin analogs; Cytotoxic agents.