TY - JOUR
T1 - Synthesis and highly potent hypolipidemic activity of alpha-asarone- and fibrate-based 2-acyl and 2-alkyl phenols as HMG-CoA reductase inhibitors
AU - Mendieta, Aarón
AU - Jiménez, Fabiola
AU - Garduño-Siciliano, Leticia
AU - Mojica-Villegas, Angélica
AU - Rosales-Acosta, Blanca
AU - Villa-Tanaca, Lourdes
AU - Chamorro-Cevallos, Germán
AU - Medina-Franco, José L.
AU - Meurice, Nathalie
AU - Gutiérrez, Rsuini U.
AU - Montiel, Luisa E.
AU - Cruz, María Del Carmen
AU - Tamariz, Joaquín
N1 - Publisher Copyright:
© 2014 Elsevier Ltd. All rights reserved.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - 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.
AB - 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.
KW - Docking 2-Acyl phenols 2-Alkyl phenols
KW - HMG-CoA reductase
KW - Hypolipidemic
KW - Phenoxyacetic
UR - http://www.scopus.com/inward/record.url?scp=84908433191&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2014.09.022
DO - 10.1016/j.bmc.2014.09.022
M3 - Artículo
SN - 0968-0896
VL - 22
SP - 5871
EP - 5882
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 21
ER -