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

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.