The manifestation of bacterial UTI (Urinary Tract Infection) has been predominantly endemic, globally; eventually, the development of new UTI antibacterial agent(s) remains the call of the day. Herein, two series of Mannich-based 4-hydroxy coumarin derivatives, 7a-m and 8a-m were designed by suitable heterocyclic amines condensed with aldehydes. The synthesised molecules were interpreted by 1H-NMR and 13C-NMR spectral analyses with in vitro antibacterial studies. The compound, 4-hydroxy-3-((4-hydroxy-3-methoxyphenyl)(morpholino)methyl)-2H-chromen-2-one8l was the significant derivative against pathogenic bacteria Staphylococcus aureus and Escherichia coli with MIC values 12.50 and 25 µM, respectively. Computational assessments with the Lipinski’s rule of five, ADMET properties and molecular docking studies revealed that analogues, 7f, 7l, 8d, 8j and 8k could be potent druggable molecules with significant binding affinity towards bacterial tyrosine kinase, as target. To understand the mode of binding and intrinsic stabilities of potent receptor-ligand complexes, each system was subjected molecular dynamics simulations for 100 ns. Inter-molecular contact analysis and intrinsic hydrogen-bond stability portrayed the analogues 8l form a number of non-bonded contacts with the receptor tyrosine kinase being mostly dominated by electrostatic and hydrophobic contacts. The results from the present structure-based designing approach might be a valuable tool towards identification of a new antibacterial drug candidate(s) against UTI in near future.