Synthesis and highly potent hypolipidemic activity of alpha-asarone- and fibrate-based 2-acyl and 2-alkyl phenols as HMG-CoA reductase inhibitors

Aarón Mendieta, Fabiola Jiménez, Leticia Garduño-Siciliano, Angélica Mojica-Villegas, Blanca Rosales-Acosta, Lourdes Villa-Tanaca, Germán Chamorro-Cevallos, José L. Medina-Franco, Nathalie Meurice, Rsuini U. Gutiérrez, Luisa E. Montiel, María Del Carmen Cruz, Joaquín Tamariz

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

In the search for new potential hypolipidemic agents, the present study focused on the synthesis of 2-acyl phenols (6a-c and 7a-c) and their saturated side-chain alkyl phenols (4a-c and 5a-c), and on the evaluation of their hypolipidemic activity using a murine Tyloxapol-induced hyperlipidemic protocol. The whole series of compounds 4-7 greatly and significantly reduced elevated serum levels of total cholesterol, LDL-cholesterol, and triglycerides, with series 6 and 7 showing the greatest potency ever found in our laboratory. At the minimum dose (25 mg/kg/day), the latter compounds lowered cholesterol by 68-81%, LDL by 72-86%, and triglycerides by 59-80%. This represents a comparable performance than that shown by simvastatin. Experimental evidence and docking studies suggest that the activity of these derivatives is associated with the inhibition of HMG-CoA reductase.

Original languageEnglish (US)
Pages (from-to)5871-5882
Number of pages12
JournalBioorganic and Medicinal Chemistry
Volume22
Issue number21
DOIs
StatePublished - Nov 1 2014

Keywords

  • Docking 2-Acyl phenols 2-Alkyl phenols
  • HMG-CoA reductase
  • Hypolipidemic
  • Phenoxyacetic

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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    Mendieta, A., Jiménez, F., Garduño-Siciliano, L., Mojica-Villegas, A., Rosales-Acosta, B., Villa-Tanaca, L., Chamorro-Cevallos, G., Medina-Franco, J. L., Meurice, N., Gutiérrez, R. U., Montiel, L. E., Cruz, M. D. C., & Tamariz, J. (2014). Synthesis and highly potent hypolipidemic activity of alpha-asarone- and fibrate-based 2-acyl and 2-alkyl phenols as HMG-CoA reductase inhibitors. Bioorganic and Medicinal Chemistry, 22(21), 5871-5882. https://doi.org/10.1016/j.bmc.2014.09.022