Quinoline-linked Pyrimidine Hybrids: Synthesis, High-performance Liquid Chromatography-based Purity Profiling,and Multimodal Biological Evaluation asa Potent Cyclooxygenase-2-Targeting Anti-Inflammatory Agent

Abstract

Introduction: Inflammation is a major pathological condition associated with several chronic disorders, and selective cyclooxygenase-2 (COX-2) enzyme inhibition is considered an effective strategy for developing safer
anti-inflammatory medications. In this study, novel quinoline-linked pyrimidine derivatives were developed, and their potential to reduce inflammation was studied. Materials and Methods: The synthesized derivatives were characterized by analytical techniques. The protein denaturation and COX inhibition assays were performed to assess
in vitro anti-inflammatory efficacy. The in vivo anti-inflammatory potential was assessed using the carrageenaninduced paw edema and cotton pellet-induced granuloma models in Wistar rats. Histopathological evaluation and ulcerogenic assessment were also performed. Results and Discussion: Several synthesized derivatives demonstrated potential anti-inflammatory properties in in vitro investigations, along with preferential COX-2 inhibition over COX-1. One of the derivatives significantly reduced paw edema volume and granuloma development in experimental
models. Histopathological studies demonstrated a near-normal tissue framework, and ulcer evaluation showed a lack of gastric mucosal damage and ulcers. The observed anti-inflammatory activity may be linked with preferential COX-2 inhibition and structural features of quinoline pyrimidine hybrids. Conclusion: The present study suggests that quinoline-linked pyrimidine hybrids possess favorable anti-inflammatory potential without ulcerogenic liability and could be used as possible lead candidates for the creation of safer anti-inflammatory drugs.