Purin-6-yl and Purin-2-yl Benzenesulphonamides and their in silico Anti Inflammatory Properties

Sulphonamides are important pharmacophores in medicinal chemistry due to their broad spectrum of biological activities and anti-inflammatory effects. This study reports the synthesis, characterization, and molecular docking of two novel sulphonamide derivatives (N-(9H-purin-6-yl)benzenesulphonamide and N-(6-oxo-6,9-dihydro-1H-purin-2-yl)benzenesulphonamide). The compounds were produced by the sulphonylation of adenine and guanine with benzenesulphonyl chloride, and characterized by melting point determination, UV-Visible spectroscopy, and FTIR spectroscopy. Molecular docking was performed against Interleukin-1-beta converting enzyme (1ICE), Tumor necrosis factor-alpha inducing protein (2AZ5), with diclofenac serving as the standard drug. The in silico assay showed strong binding affinities, with N-(6-oxo-6,9-dihydro-1H-purin-2-yl)benzenesulphonamide showing the highest binding energy (-6.9 kcal/mol for 1ICE and -7.5 kcal/mol for 2AZ5), surpassing diclofenac in both targets. These findings suggest that the synthesized derivatives, particularly the guanine-based analogue, possess significant potential as lead compounds for anti-inflammatory drug development.