Development and Biological Evaluation of Novel Spiro 4‐Chromanones as Potent Quorum Sensing Inhibitors

Abstract

Infectious diseases are an integral part of human life and have the potential to cause significant damage to life. Currently, antimicrobial agents are no longer effective, as most human pathogenic microbes have developed various methods and strategies to inactivate or inhibit the antimicrobial action. Hence, WHO has asked global researchers to explore new antimicrobial agents with a unique mechanism of action or target to overcome this global silent pandemic of bacterial resistance. Quorum sensing, a universal bacterial communication mechanism, plays a pivotal role in pathogenesis and disease spread. We in this work explored the quorum sensing mechanism as one of the potential targets for treating bacterial infections. We designed and synthesized a series of novel analogues of 7‐(4‐(amino methyl) phenyl) spiro [chromane‐2,4′‐piperidin]‐4‐one hydrochloride (D 1–18) with m‐bromo‐o‐hydroxyacetophenone as starting material. Three compounds (D7, D9, and D11) showed the most promising antiquorum sensing activity against the golden standard QS indicator strain Chromobacterium violaceum ATCC 12472 at ≤50 µg/mL. Cytotoxicity of the active compounds was tested against the human macrophages using cell viability and cell death as an indicator using MTT assay and LDH assay at 50 and 100 µg/mL. Molecular docking studies revealed significant binding affinity towards the catalytic site of amino acids of the target protein. From the abovementioned studies, we can infer that the synthesized derivatives can be novel leads in the generation of novel QS inhibitors.