Synthesis of a new diarylhydrazone derivative and an evaluation of its in vitro biofilm inhibition and quorum sensing disruption along with a molecular docking study

Abstract

Molecules that target quorum sensing and biofilm inhibition are useful antimicrobials. In this regard, a new diarylhydrazone was synthesized and characterized using infrared, high-resolution mass spectrometry and nuclear magnetic resonance experiments as N-[(E)-4-bromo-2,5-diheptyloxybenzylideneamino]-2,4-dinitroaniline (BHBANA). Minimal inhibitory concentrations (MICs) vary from 0.625 to 2.5 mg mL−1. This compound was screened in vitro for its inhibition of quorum sensing–mediated violacein production by Chromobacterium violaceum CV12472 at MIC and sub-MIC and showed percentage inhibition varying from 100% at MIC to 5.7% ± 0.2% at MIC/32. Against Chromobacterium violaceum CV026, BHBANA exhibited anti-quorum-sensing zone diameters of 10.5 ± 0.3 mm and 7.0 ± 0.1 mm at MIC and MIC/2, respectively. BHBANA shows concentration-dependent inhibition of swarming motility on flagellated Pseudomonas aeruginosa PA01 with the highest % inhibition of 28.30% ± 0.50% μg mL−1 at MIC. The product inhibits biofilm formation, with the best biofilm inhibition being observed against Staphylococcus aureus varying from 72.24% ± 0.86% (MIC) to 09.82% ± 0.10% (MIC/8). Molecular docking studies carried out utilizing the Schrodinger software identified interactions between BHBANA and different receptor compartments of Chromobacterium violaceum, which can block pathogenic gene expression. The results suggest the potential of BHBANA in reducing microbial virulence.