Design and Evaluation of Synthesized Pyrrole Derivatives as Dual COX-1 and COX-2 Inhibitors Using FB-QSAR Approach

Abstract

This study delves into the intricate dynamics of the inflammatory response, unraveling the pivotal role played by cyclooxygenase (COX) enzymes, particularly COX-1 and COX-2 subtypes. Motivated by the pursuit of advancing scientific knowledge, our contribution to this field is marked by the design and synthesis of novel pyrrole derivatives. Crafted as potential inhibitors of COX-1 and COX-2 enzymes, our goal was to unearth molecules with heightened efficacy in modulating enzyme activity. A meticulous exploration of a synthesis library, housing around 3000 compounds, expedited the identification of potent candidates. Employing advanced docking studies and field-based Quantitative Structure-Activity Relationship (FB-QSAR) analyses enriched our understanding of the complex interactions between synthesized compounds and COX enzymes. Guided by FB-QSAR insights, our synthesis path led to the identification of compounds 4g, 4h, 4l, and 4k as potent COX-2 inhibitors, surpassing COX-1 efficacy. Conversely, compounds 5b and 5e exhibited heightened inhibitory activity against COX-1 relative to COX-2. The utilization of pyrrole derivatives as COX enzyme inhibitors holds promise for groundbreaking advancements in the domain of anti-inflammatory therapeutics, presenting avenues for innovative pharmaceutical exploration.