Executive Summary : | Pseudomonas aeruginosa is a Gram-negative, rod-shaped, facultative-anaerobe bacteria that causes mild to life-threatening infections. Due to antibiotic resistance, novel antimicrobials are urgently needed to treat this global priority pathogen. Isatin and Indole are two important molecules with numerous implications in drug discovery. Recent reports reveal that isatin and indole derivatives possess antiviral, antibacterial, anti-inflammatory, antifungal, anticancer, anti-HIV, anti-mycobacterial, anti-malarial, and antioxidant activities. These derivatives exhibited significant antimicrobial activity on resistant pathogens like P. aeruginosa, Methicilin-resistant Staphylococcus aureus (MRSA), Mycobacterium tuberculosis, and other bacteria. This project used a molecular hybridization probe to conjugate Isatin and Indole moieties for developing novel isatin-indole hybrids, specifically aiming to inhibit the pyruvate kinase activity of P. aeruginosa. The designed hybrids were first checked for their interaction with the pyruvate kinase enzyme by molecular docking analysis. Ten isatin-indole hybrids were synthesized, characterized, and confirmed by spectral analysis methods. Bio-assays revealed excellent antibacterial activity of some isatin-indole hybrids (MIC ranging between 2.5-25µM) compared to Oxacillin (beta-lactam antibiotic, MIC-12.5 µM). Some active compounds also exhibited antimicrobial activity on MRSA and M. tuberculosis at higher concentrations. The study focuses on synthesizing more isatin-indole hybrids, their complete antimicrobial evaluation on P. aeruginosa, and biochemical characterization of the hybrids on the pyruvate kinase protein. |