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 - Funding Information:
We thank Bruce Allan Larsen for reviewing the use of English in this manuscript. M.C.C. and J.T. gratefully acknowledge Secretaría de Investigación y Posgrado (SIP)-IPN (Grants 20090326 , 20100236 , 20110172 , 20120830 , 20130686 , and 20140858 ) and CONACYT (Grants 80508, 83446 , and 178319 ) for financial support. A.M., A.M.-V., B.R.-A., R.U.G. and L.E.M. thank CONACYT for graduate scholarships awarded and also thank SIP-IPN (PIFI) for a scholarship complement. A.M. also thanks CONACYT (Grant 178319) for a partial scholarship. F.J., L.G.-S., L.V.-T., G.C.-C., M.C.C. and J.T. are fellows of the Estímulos al Desempeño de los Investigadores (EDI)-IPN and Comisión de Operación y Fomento de Actividades Académicas (COFAA)-IPN programs.
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
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U2 - 10.1016/j.bmc.2014.09.022
DO - 10.1016/j.bmc.2014.09.022
M3 - Article
C2 - 25311563
AN - SCOPUS:84908433191
SN - 0968-0896
VL - 22
SP - 5871
EP - 5882
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 21
ER -