Design, synthesis and biological evaluation of 1, 2, 3-triazole based 2-aminobenzimidazoles as novel inhibitors of LasR dependent quorum sensing in Pseudomonas aeruginosa. Issue 50 (17th September 2019)

• Record Type: Journal Article
• Authors: Srinivasarao, Singireddi; Nandikolla, Adinarayana; Nizalapur, Shashidhar; Yu, Tsz Tin; Pulya, Sravani; Ghosh, Balaram; Murugesan, Sankaranarayanan; Kumar, Naresh; Chandra Sekhar, Kondapalli Venkata Gowri
• Is Part Of: RSC advances. Volume 9:Issue 50(2019)
• Page Start: 29273
• Page End: 29292
• Publication Date: 2019-09-17
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c9ra05059k
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Out of 40 benzimdazoles, 12 exhibited potent QSI activity against P. aeruginosa 6p, most active QSI is docked to LasR and is less toxic against HEK 293 cell line. Abstract : Bacteria regulate their phenotype, growth and population via a signalling pathway known as quorum sensing. In this process, bacteria produce signalling molecules (autoinducers) to recognize their population density. Inhibiting this quorum sensing signalling pathway is one of the potential methods to treat bacterial infection. 2-Aminobenimdazoles are reported to be the strongest inhibitors of quorum sensing against wild-type P. aeruginosa . 1, 2, 3-Triazole based acyl homoserine lactones are found to be good inhibitors of the quorum sensing LasR receptor. Hence, in our current study, forty 1, 2, 3-triazole based 2-aminobenzimdazoles were synthesized and characterized using IR, NMR, MS and elemental analysis. A single crystal was developed for N -(1 H -benzo[ d ]imidazol-2-yl)-2-(4-nonyl-1 H -1, 2, 3-triazol-1-yl)acetamide (6d ). All final compounds were screened for in vitro quorum sensing inhibitory activity against Pseudomonas aeruginosa . The quorum sensing inhibitory activity was determined in the LasR expressing P. aeruginosa MH602 reporter strain by measuring green fluorescent protein production. Among the title compounds, N -(1 H -benzo[ d ]imidazol-2-yl)-2-(4-(4-chlorophenyl)-1 H -1, 2, 3-triazol-1-yl)acetamide (6i ) exhibited good quorum sensing inhibitory activity of 64.99% at 250 μM. N -(1 H -Benzo[ d ]imidazol-2-yl)-2-(4-(4-nitrophenyl)-1 H -1, 2, 3-triazol-1-yl)acetamide (6p ) exhibited the most promising quorum sensing inhibitory activity with 68.23, 67.10 and 63.67% inhibition at 250, 125 and 62.5 μM, respectively. N -(1 H -Benzo[ d ]imidazol-2-yl)-2-(4-(4-(trifluoromethyl)phenyl)-1 H -1, 2, 3-triazol-1-yl)acetamide (6o ) and N -(5, 6-dimethyl-1 H -benzo[ d ]imidazol-2-yl)-2-(4-(4-(trifluoromethyl)phenyl)-1 H -1, 2, 3-triazol-1-yl)acetamide (7l ) also exhibited 64.25% and 65.80% quorum sensing inhibition at 250 μM. Compound6p, the most active quorum sensing inhibitor, also displayed low cytotoxicity at the tested concentrations (25, 50 and 100 μM) against normal human embryonic kidney cell lines. Finally, a docking study using Schrodinger Glide elucidated the possible putative binding mode of the significantly active compound6p at the active site of the target LasR receptor (PDB ID: ;2UV0 ).