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• W1759546898 abstract "Drugs affecting more than one target could result in a more efficient treatment of multifactorial diseases as well as fewer safety concerns, compared to a one-drug one-target approach. Within our continued efforts towards the design of multifunctional molecules against atherosclerosis, we hereby report the synthesis of 17 new morpholine derivatives which structurally vary in terms of the aromatic substitution on the morpholine ring. These derivatives simultaneously suppress cholesterol biosynthesis through SQS inhibition (IC50 values of the most active compounds are between 0.7 and 5.5 μM) while exhibiting a significant protection of hepatic microsomal membranes against lipid peroxidation (with IC50 values for the most active compounds being between 73 and 200 μM). Further evaluation of these compounds was accomplished in vivo in an animal model of acute experimental hyperlipidemia, where it was observed that compounds reduced the examined lipidemic parameters (TC, TG and LDL) by 15-80%. In order to examine the mode of binding of these molecules in the active catalytic site of SQS, we also performed docking simulation studies. Our results indicate that some of the new compounds can be considered interesting structures in the search for new multifunctional agents of potential application in atherosclerosis." @default.
• W1759546898 created "2016-06-24" @default.
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• W1759546898 date "2015-11-01" @default.
• W1759546898 modified "2023-09-26" @default.
• W1759546898 title "Antihyperlipidemic morpholine derivatives with antioxidant activity: An investigation of the aromatic substitution" @default.
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• W1759546898 doi "https://doi.org/10.1016/j.bmc.2015.09.034" @default.
• W1759546898 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26433631" @default.
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