Evaluation of Novel Isatin–Schiff Base Derivatives: Monoamine Oxidase Inhibition and Antimicrobial Assessment

Five novel series of isatin–Schiff base derivatives ( 1a–5e ) were synthesized, and their neuroprotective and anti‐infective potential was evaluated. Their half‐maximal inhibitory concentration (IC ₅₀ ) was determined against both monoamine oxidase A (MAO‐A) and MAO‐B targets for the treatment of depression and Parkinson's disease, respectively. The anti‐infective potential of the synthesized derivatives was evaluated by measuring their IC ₅₀ values against urease, an enzyme utilized by specific pathogenic bacteria as a virulence factor. The minimum inhibitory concentration for each compound was assessed against a panel of human pathogens. Most derivatives had potent in vitro activity against MAO‐A and MAO‐B, even greater than the positive control, isatin. The 4‐chloroisatin substituted series ( 2a – d ) showed exceptional MAO‐A inhibition ( 2d : 0.040 ± 0.002 µM), while the unsubstituted, 5‐, 6‐, and 7‐chloroisatin analogues ( 1a – e , 3a – c , 4a – b , and 5a – e ) demonstrated high potency and selectivity toward MAO‐B, the most active being 5d (0.018 ± 0.003 µM; selectivity index = 15 389). Kinetic analysis confirmed a competitive and reversible mode of inhibition. None of the derivatives showed urease inhibition or significant antibacterial activity. These findings highlight the isatin–Schiff base derivatives as promising agents for potent and selective MAO inhibitors with therapeutic potential for neurodegenerative disorders.