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

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• 作者：Chi B. Vu ; Jean E. Bemis ; Ericka Benson ; Pradeep Bista ; David Carney ; Richard Fahrner ; Diana Lee ; Feng Liu ; Pallavi Lonkar ; Jill C. Milne ; Andrew J. Nichols ; Dominic Picarella ; Adam Shoelson ; Jesse Smith ; Amal Ting ; Allison Wensley ; Maisy Yeager ; Michael Zimmer ; Michael R. Jirousek
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：February 11, 2016
• 年：2016
• 卷：59
• 期：3
• 页码：1217-1231
• 全文大小：714K
• ISSN：1520-4804

文摘

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 <b>5b> 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 <b>11b> 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.