Hexadecanoic acid analogs as potential CviR-mediated quorum sensing inhibitors in Chromobacterium violaceum : an in silico study

Chromobacterium violaceum is a Gram-negative, rod-shaped and opportunistic human pathogen. C. violaceum is resistant to various antibiotics due to the production of quorum sensing (QS)-controlled virulence factor and biofilm formation. Hence, we need to find alternative strategies to overcome the antimicrobial resistance and biofilm formation in Gram-negative bacteria. QS is a mechanism in which bacteria's ability to regulate the virulence factors and biofilm formations leads to disease progression. Previously, hexadecanoic acid was identified as a CviR-mediated quorum-sensing inhibitor. In this study, we aimed to discover potential analogs of hexadecanoic acid as a CviR-mediated quorum-sensing inhibitor against C. violaceum by using ADME/T prediction, density functional theory, molecular docking, molecular dynamics and free energy binding calculations. ADME/T properties predicted for analogs were acceptable for human oral absorption and feasibility. The highest occupied molecular orbitals and lowest unoccupied molecular orbitals gap energies predicted and found oleic acid with -0.3748 energies. Docosatrienoic acid exhibited the highest binding affinity -8.15 Kcal/mol and strong and stable interactions with the amino acid residues on the active site of the CviR protein. These compounds on MD simulations for 100 ns show strong hydrogen-bonding interactions with the protein and remain stable inside the active site. Our results suggest hexadecanoic acid analogs could serve as anti-QS and anti-biofilm molecules for treating C. violaceum infections. However, further validation and investigation of these inhibitors against CviR are needed to claim their candidacy for clinical trials.Communicated by Ramaswamy H. Sarma.