Design and Synthesis of Novel NSAID Hybrid Conjugates as Potential Anti-inflammatory

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 maintaining the integrity of the stomach lining as well as proper kidney function. Inhibition of this enzyme system can lead to stomach ulcers and kidney 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 nuclear magnetic resonance and infrared spectroscopy. Biological studies indicate that some of the synthesized compounds are showing improved potency when compared to ibuprofen alone as well as decreased ulcer formation.