Quorum sensing is a well-known term for describing bacterial cell–cell communication. Bacteria use quorum sensing pathways to respond to external factors such as nutrient availability, defense mechanisms, and coordinate host toxic behaviors such as biofilm formation, virulence production, and other pathogenesis. Discovery of novel compounds which inhibit quorum sensing without being antibiotic are currently emerging fields. Herein, the library of fifteen benzo[d]thiazole/quinoline-2-thiol bearing 2-oxo-2-substituted-phenylethan-1-yl compounds was designed, synthesized and evaluated to find novel quorum sensing inhibitors. Firstly, compounds were evaluated for their growth inhibitory activities at high concentrations up to 1000 μg mL⁻¹ toward Pseudomonas aeruginosa. Under our conditions, twelve compounds showed moderate growth inhibitory activities in the concentration tested. To our delight, three compounds 3, 6 and 7 do not affect the growth of the bacteria which were chosen for the evaluation of quorum sensing inhibitor activities. In the LasB system, our compounds 3, 6, 7 showed promising quorum-sensing inhibitors with IC₅₀ of 115.2 μg mL⁻¹, 182.2 μg mL⁻¹ and 45.5 μg mL⁻¹, respectively. In the PqsR system, no activity observed suggesting that the selectivity of the compound toward the LasB system. In addition, 7 showed the moderate anti-biofilm formation of Pseudomonas aeruginosa. Docking studies revealed that 3, 6 and 7 binding to the active site of Pseudomonas aeruginosa quorum sensing LasR system with better affinity compared to reference compounds 4-NPO. Finally, computation calculations suggest that compounds are a good template for further drug development.