Synthesis and Characterization of Fatty Acid Conjugates of Niacin and Salicylic Acid

Journal of Medicinal Chemistry
Chi B VuMichael R Jirousek

Abstract

This report describes the synthesis and preliminary biological characterization of novel fatty acid niacin conjugates and fatty acid salicylate conjugates. These molecular entities were created by covalently linking two bioactive molecules, either niacin or salicylic acid, to an omega-3 fatty acid. This methodology allows the simultaneous intracellular delivery of two bioactives in order to elicit a pharmacological response that could not be replicated by administering the bioactives individually or in combination. The fatty acid niacin conjugate 5 has been shown to be an inhibitor of the sterol regulatory element binding protein (SREBP), a key regulator of cholesterol metabolism proteins such as PCSK9, HMG-CoA reductase, ATP citrate lyase, and NPC1L1. On the other hand, the fatty acid salicylate conjugate 11 has been shown to have a unique anti-inflammatory profile based on its ability to modulate the NF-κB pathway through the intracellular release of the two bioactives.

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Citations

Feb 12, 2020·Drug Metabolism Reviews·Hanlan LiuChandra Prakash
Jun 20, 2020·Medicinal Research Reviews·Claudia AlbertiniMaria L Bolognesi
Mar 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Claudia AlbertiniMaria Laura Bolognesi
Aug 2, 2017·Neuromuscular Disorders : NMD·Leanne M WardUNKNOWN Parent Project Muscular Dystrophy Bone Health Workshop Collaborators
Apr 4, 2020·Journal of Natural Products·Thomas WongZhe-Sheng Chen
Dec 18, 2020·ACS Medicinal Chemistry Letters·Michele RossiMaria Laura Bolognesi
Aug 14, 2020·Journal of Medicinal Chemistry·Skylar J Ferrara, Thomas S Scanlan

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