Synthesis, Biocidal and Antibiofilm Activities of New Isatin-Quinoline Conjugates against Multidrug-Resistant Bacterial Pathogens along with Their In Silico Screening.

Isatin-quinoline conjugates - and - were assembled by the reaction of N-(bromobutyl) isatin derivatives , with aminoquinolines - and their corresponding hydrazinyl - in good yields. The structures of the resulting conjugates were established by spectroscopic tools and showed data consistent with the proposed structures. In vitro antibacterial activity against different bacterial strains was evaluated. All tested conjugates showed significant biocidal activity with lower MIC than the first line drugs chloramphenicol and ampicillin. Conjugates , and displayed the most potent activity against all clinical isolates. The antibiofilm activity for all tested conjugates was screened against the reference drug vancomycin using the strain. The results revealed that all conjugates had an inhibitory activity against biofilm formation and conjugate. Conjugate showed 83.60% inhibition at 10 mg/mL. In addition, TEM studies were used to prove the mechanism of antibacterial action of conjugates and against (). Modeling procedures were performed on - and - and interestingly the results were nearly consistent with the biological activities. In addition, in silico pharmacokinetic evaluation was performed and revealed that the synthesized compounds - and - were considered drug-like molecules with promising bioavailability and high GI absorption. The results confirmed that the title compounds caused the disruption of bacterial cell membranes and could be used as potential leads for the further development and optimization of antibacterial agents.