The continuous intake of a specific antibiotic for diseases is continuously reducing the immunity of the human in course of time, which includes Covid-19 treatment. Recent research on Schiff bases shows the promising biological activities and good antibacterial results. In this study, three Schiff bases with lactam ring using isatin and three different anisidines in presence of acetic acid were synthesized and characterized. Drug likeness was examined using Molsoft and docking against the target proteins such as 5J6R, 3L9L, 5HVY, Covid main protease and 3ZBO proteins for drug suitability. The experimental antibacterial activity against Gram-positive strains like Staphylococcus aureus, Bacillus subtilis and Staphylococcus epidermidis. Among the synthesized compounds, three Schiff bases ortho and meta substituted compounds exhibited good results when compared to para compound, where the methoxyl group position effect was observed. © 2021 Elsevier B.V., All rights reserved.