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In this study, the authors designed and synthesized a total of 33 β‐nitrostyrene derivatives using 1‐nitro‐2‐phenylethane (NPe) as the lead compound, to target the facultative anaerobic bacterial pathogen Serratia marcescens. The QS‐inhibitory effects of these compounds were evaluated using S. marcescens NJ01 and the reporter strain Chromobacterium violaceum CV026. Among the 33 new β‐nitrostyrene derivatives, (E)‐1‐methyl‐4‐(2‐nitrovinyl)benzene (m‐NPe, compound 28) was proven to be a potent inhibitor that reduced biofilm formation of S. marcescens NJ01 by 79%. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) results revealed that treatment with m‐NPe (50 μg/mL) not only enhanced the susceptibility of the formed biofilms but also disrupted the architecture of biofilms by 84%. Molecular dynamics analysis showed that m‐NPe could bind stably to SmaR. Importantly, a microscale thermophoresis (MST) test revealed that SmaR could be a target protein for the screening of a quorum sensing inhibitor (QSI) against S. marcescens. Overall, this study highlights the efficacy of m‐NPe in suppressing the virulence factors of S. marcescens, identifying it as a new potential QSI and antibiofilm agent capable of restoring or improving antimicrobial drug sensitivity.
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Wang J, Yang J‐Y, Durairaj P, Wang W, Wei D‐Y, Tang S, et al
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