A green synthesis of quinoline-4-carboxylic derivatives using p-toluenesulfonic acid as an efficient organocatalyst under microwave irradiation and their docking, molecular dynamics, ADME-Tox and biological evaluation

P-Toluenesulfonic acid, being an efficient, nonhazardous, and fast accessible organocatalyst, was used for the preparation of quinoline-4-carboxylic acid derivatives via a one-pot three-component reaction of aromatic benzaldehyde, substituted aniline, and pyruvic acid under microwave irradiation. After completion of the reaction, the pure products were isolated by column chromatography. Here, to achieve the desired synthesis, various catalytic and solvent conditions were applied to perform a comparison study. We are using higher yield, simple work-up process, avoiding the use of hazardous organic solvents, short reaction time and higher advantages of the present protocol in the study. Biological activities of synthesized compounds were tested against various antibacterial, antifungal, antimalarial, and antituberculosis strains. Compounds 4a and 4c (MIC 50 mu g/mL) and compounds 4d and 4n (MIC 62.5 mu g/mL) were found active against the Escherichia coli strain, compounds 4c and 4p (MIC 25 mu g/mL) were found active against the Staphylococcus aureus strain, and compounds 4c and 4d were found active against the Plasmodium falciparum strain. Molecular docking revealed that ligands and proteins fitted exactly in the binding pocket and had significant correlation with the biological activity. We have also tested molecular dynamics and ADME-Tox parameters for the synthesized compounds.