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 (IC₅₀) 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 IC₅₀ 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.