Rational drug design, synthesis, and in vivo biological activity of new indolyl-imidazolone hybrids as potential and safer non-steroidal anti-inflammatory agents

The study aimed to synthesize and evaluate the potential anti-inflammatory analgesic activities of rationally designed hybrid molecules imidazolone indole nuclei linked through a methylene bridge. Indolyl-imidazolone hybrids were synthesized in three simple steps starting from 2-phenyl-1 H -indole ( 1 ). In first step, compound was converted -indole-3-carbaldehyde 2 ) using standard conditions Vilsmeier Haack reaction. Benzoyl glycine reacted with (step 2) followed by treatment aromatic/aliphatic amines 3) furnish indolyl-imidazolone hybrids. vivo activity along ulcerogenicity prepared evaluated experimental animals. Molecular properties pharmacokinetic profile also predicted online computational software. Cyclooxygenase-2 (COX-2) enzyme (PDB: 3pgh) used for molecular docking studies. Indomethacin aspirin as reference compounds comparison purpose. percentage inhibition edema rats reduction frequency acetic acid induced writhes mice indicated that two namely 3-(3-Hydroxpropyl)-2-phenyl-5-[(2-phenyl-1 -indol-3-yl)methylene]-4 -imidazol-4-one 4g 3-(2,4-Dinitrophenyl)-2-phenyl-5-[(2-phenyl-1 -indol-3-yl) methylene]- 4 4b could be useful treating pain inflammatory conditions. Both exhibited better biological spectrum than drug indomethacin. Additionally, both potent noted less ulcerogenic Pharmacokinetic ADMETsar SwissADME cheminformatic software orally bioavailable high blood brain barrier permeability. However, studies revealed binds COX-2 more strongly lower binding energy formation hydrogen bond interactions amino residues pocket. It concluded are promising lead candidates should further studied develop