Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium implicated in acute and chronic nosocomial infections and a leading cause of patient mortality. Pseudomonas aeruginosa infections are frequently associated with the development of biofilms, which give the bacteria additional drug resistance and increase their virulence. The goal of this study was to find strong compounds that block the Anthranilate-CoA ligase enzyme made by the pqsA gene. This would stop the P. aeruginosa quorum signaling system. This enzyme plays a crucial role in the pathogenicity of P. aeruginosa by producing autoinducers for cell-to-cell communication that lead to the production of biofilms. Pharmacophore-based virtual screening was carried out utilizing a library of commercially accessible enzyme inhibitors. The most promising hits obtained during virtual screening were put through molecular docking with the help of MOE. The virtual screening yielded 7/160 and 10/249 hits (ZINC and Chembridge). Finally, 2/7 ZINC hits and 2/10 ChemBridge hits were selected as potent lead compounds employing diverse scaffolds due to their high pqsA enzyme binding affinity. The results of the pharmacophore-based virtual screening were subsequently verified using a molecular dynamic simulation-based study (MDS). Using MDS and post-MDS, the stability of the complexes was evaluated. The most promising lead compounds exhibited a high binding affinity towards protein-binding pocket and interacted with the catalytic dyad. At least one of the scaffolds selected will possibly prove useful for future research. However, further scientific confirmation in the form of preclinical and clinical research is required before implementation.

In organic chemistry, the umpolung reaction is an important concept that significantly expands the chemical space and provides unique structures. Although prior research focused on constructing complex molecular frameworks using phase transfer catalysts, the umpolung reaction is well known for its roles in 1,4-conjugate addition and Stetter reactions. Herein, we reported a novel enzymatic approach using immobilized transaminase CV2025 to catalyze the umpolung conjugate addition reaction. This method facilitates the nucleophilic addition of 2-(nitrophenyl)-N-(trifluoromethyl) imine to cyclopentanone, efficiently synthesized a complex imine and its derivatives up to 78% yield. Unlike traditional methods, this enzymatic strategy eliminates the need of a transition metal or chemical (acid, base) catalyst, broadens the substrate scope, and operates under milder conditions. Mechanistic studies, supported by molecular dynamics calculations and alanine scanning mutagenesis, identified key residues influencing regioselectivity. This study presents a sustainable, enzyme-catalyzed method for constructing complex frameworks with broad potential in pharmaceutical synthesis and beyond.