Design, Synthesis, and Anti-inflammatory Studies of NSAID Hybrid Conjugates

Abstract

Non-steroidal anti-inflammatory drugs are one of the most common drugs administered worldwide as highly effective analgesic, antipyretic and anti-inflammatory agents. The drugs function by inhibiting the COX-2 enzyme system which leads to a decrease in inflammation; however, the drugs also inhibit the COX-1 enzyme system which is critical to normal renal function, gastric mucosal integrity, vascular homeostasis, and the autocrine response to circulating hormones which can lead to gastric ulcers and renal dysfunction. Hybrid conjugates of existing non-steroidal anti-inflammatory drugs (NSAIDs) have already been synthesized with Ibuprofen, Acetaminophen, and amino acids to increase potency and decrease toxicity. Computational chemistry studies of these compounds show that the free phenol moiety in acetaminophen plays a greater role in the inhibition of the COX 2 enzyme system than the amine moiety. The previous compounds utilized the phenol moiety to form the product. New hybrid conjugates of Ibuprofen and Acetaminophen via amino acid linkers have been synthesized, leaving the phenol moiety free. The compounds have been characterized by NMR and IR. Biological studies indicate that some of the synthesized compounds are showing improved potency when compared to Ibuprofen alone. Computational chemistry studies and molecular modeling will be used to support the�in-vivo�biological activity.