Synthesis and Molecular Drug Efficacy of Indoline‐based Dihydroxy‐thiocarbamides: Inflammation Regulatory Property Unveiled over COX‐2 Inhibition, Molecular Docking, and Cytotoxicity Prospects

摘要

> In this study, substituted indoline‐based dihydroxy‐carbamides ( 5a–i ) were synthesized and evaluated as the cyclooxygenase‐2 (COX‐2) inhibitors to testify their inflammatory regulations through COX‐2 inhibition. Enzyme‐linked immunosorbent assay‐based competitive (COX‐2) inhibition ( in vitro ) followed by a molecular docking study ( in silico ) was executed to ensure the mode of interaction between 5a–i and COX‐2. Apart from COX‐2 inhibition studies, free‐radical scavenging ability (H ₂ O ₂ estimation method) and the human red blood cell membrane protection ( in vitro anti‐inflammatory) capability of the compounds 5a–i assessment were also evaluated. Excellent antimicrobial and anticancer activity exhibited by thiocarbamide substituted compounds ( 5a–d ) than carbamide ( 5e–i ). In molecular docking studies, the obtained binding affinity values of 5a–i indicated the therapeutic selectivity on COX‐2 (PDB ID: 1CX2) over COX‐1 (PDB ID: 1EQG). Established inhibitory constant ( ki ) values were found as low as in nanomolar/picomolar against COX‐2. Reliable COX‐2 inhibition of 78–92% and IC ₅₀ 0.002–1.28?μ M were obtained. Human red blood cell membrane was found to be effectively stabilized/protected by 5a–i up to 98%. Excellent antioxidant property (average radical scavenging 92%) and structure–activity relationship predictions confirmed the druggability potentials of 5a–i as effective, future anti‐inflammatory drugs. The cytotoxicity