Synthesis and highly potent hypolipidemic activity of alpha-asarone- and fibrate-based 2-acyl and 2-alkyl phenols as HMG-CoA reductase inhibitors |
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Institution: | 1. Toxicology Graduate Program, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada;2. Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK S7N 5B2, Canada;3. Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada;4. Department of Soil Science, University of Saskatchewan, Saskatoon, SK S7N 5B8, Canada |
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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. |
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Keywords: | Hypolipidemic Docking 2-Acyl phenols 2-Alkyl phenols Phenoxyacetic HMG-CoA reductase |
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