DESIGN AND SYNTHESIS OF INDOLE DERIVATIVES AS COX-2 INHIBITORS FOR ANTI- INFLAMMATORY ACTIVITY

Seetaramswamy Seepana*, Dr. Vikas Verma, Dr. Pankaj Sharma, Dr. Jaya Sharma, Dr. N. Ravindra, Chintada Sowjanya, Dr. K. Sudheer Kumar, Dr. K. Ashok Babu

Indole-based compounds have gained considerable attention in medicinal chemistry due to their broad spectrum of biological activities and structural versatility. In the present study, a series of novel indole–pyrimidine derivatives (SIPA1–SIPA10) were designed, synthesized, and evaluated for their potential anti-inflammatory activity as cyclooxygenase-2 (COX-2) inhibitors. The design strategy focused on combining the indole and pyrimidine scaffolds to enhance biological activity and selectivity toward the COX-2 enzyme. The synthesized compounds were characterized using standard analytical techniques such as TLC and IR spectroscopy. In silico ADME analysis was performed using the SwissADME tool to evaluate physicochemical and pharmacokinetic properties, including molecular weight, lipophilicity, hydrogen bonding capacity, and drug-likeness based on Lipinski, Ghose, and Veber rules. Most of the synthesized compounds showed acceptable drug-like characteristics with no rule violations. The anti-inflammatory activity was assessed using the carrageenan-induced rat paw edema model, and the percentage inhibition of inflammation was measured at different time intervals. Among the tested compounds, SIPA2 and SIPA4 exhibited significant anti-inflammatory activity, showing inhibition levels comparable to the standard drug indomethacin after 4 hours. These findings suggest that the incorporation of indole and pyrimidine moieties may enhance COX-2 inhibitory activity and support further development of these derivatives as potential anti-inflammatory agents.