Influence of Available Hydrophobic Interactions in New 2‑(Propylthio)‑N‑(1,3,4-thiadiazol-2-yl)nicotinamide Pharmacophore and Evaluation of Its Therapeutic Potential

Required hydrophobic interactions exerted by the new pharmacophore 2-(propylthio)-N-(1,3,4-thiadiazol-2-yl)nicotinamide (Compound 3) were designed, synthesized, and characterized by NMR, FFT-IR, high-resolution mass spectrometry (HR-MS), and single-crystal X-ray diffraction (SC-XRD) analytical techniques. Based on the SC-XRD analysis, the pharmacophore’s surface characteristics were evaluated by Hirshfield surface analysis, and it was compared with the theoretical DFT-optimized structure. This demonstrates the structural overview of nucleophilic and electrophilic parts and the molecular electrostatic potential values in the range of −0.05547 to +0.05547. The Compound 3 drug-likeness property was validated by in silico techniques. From the molecular docking study, compound 3 has binding interactions of −7.82 kcal/mol with COX-1 and −7.08 kcal/mol with COX-2 isoforms of the cyclooxygenase enzyme. Compound 3 was explored for free-radical scavenging activity by ABTS and DPPH assays. Further, its bioefficacy was validated by using the MTT cell viability assay, COX-2, and LOX-5 enzyme inhibition. Then, the Compound 3 antibacterial efficiency was also examined by the Gram-negative and Gram-positive bacterial strains. Combining the above results, this study offers insights into the hydrophobic nature of new pharmacophore motifs and their impactful effects on biological properties.