Premium
Design, Synthesis and Biological Evaluation of Triazole‐Containing 2‐Phenylindole and Salicylic Acid as Quorum Sensing Inhibitors Against Pseudomonas aeruginosa
Author(s) -
Srinivasarao Singireddi,
Nizalapur Shashidhar,
Yu Tsz Tin,
Wenholz Daniel Stanley,
Trivedi Prakruti,
Ghosh Balaram,
Rangan Krishnan,
Kumar Naresh,
Gowri Chandra Sekhar Kondapalli Venkata
Publication year - 2018
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201801622
Subject(s) - acetamide , chemistry , stereochemistry , salicylic acid , triazole , 1,2,3 triazole , amide , benzoic acid , quorum sensing , biochemistry , organic chemistry , virulence , gene
We designed and synthesized 2‐phenylindole‐amide‐triazole and salicyclic acid‐triazole analogues and characterized using NMR, MS and elemental analysis. Furthermore, single crystal was developed for N ‐(2‐Phenyl‐1 H ‐indol‐3‐yl)‐2‐(4‐propyl‐1 H ‐1,2,3‐triazol‐1‐yl)acetamide ( 7 a ), 2‐(4‐(4‐(tert‐Butyl)phenyl)‐1 H ‐1,2,3‐triazol‐1‐yl)‐ N ‐(2‐phenyl‐1 H ‐indol‐3‐yl)acetamide ( 7 h ) and 3‐(1‐(4‐Ethylphenyl)‐1 H ‐1,2,3‐triazol‐4‐yl)‐ N ‐(2‐phenyl‐1 H ‐indol‐3‐yl)propanamide ( 10 j ). Final compounds were screened for in vitro quorum sensing inhibitory (QSI) activity against Pseudomonas aeruginosa . The QSI activity was determined in the LasR expressing P. aeruginosa MH602 reporter strain by measuring green fluorescent protein (GFP) production. 10 j , 4‐(1‐Heptyl‐1 H ‐1,2,3‐triazol‐4‐yl)‐ N ‐(2‐phenyl‐1 H ‐indol‐3‐yl)butanamide ( 11 b ) and 4‐(1‐(4‐Bromophenyl)‐1 H ‐1,2,3‐triazol‐4‐yl)‐ N ‐(2‐phenyl‐1 H ‐indol‐3‐yl)butanamide ( 11 e) exhibited promising QSI activity with 60.82, 58.89 and 54.34% at 250 μM, respectively. 1,2,3‐Triazole based salicylic acid derivatives exhibited moderate to good activity and 2‐Hydroxy‐4‐(1‐phenyl‐1 H ‐1,2,3‐triazol‐4‐yl)benzoic acid ( 17 e) is the most promising QS inhibitor with 40.28% inhibition at 250 μM. These compounds were docked into the binding site of the LasR receptor protein to understand possible binding ligand‐protein interactions. The most active compounds were subjected to cytotoxicity assay and were found to be less cytotoxic against HEK 293 cell line at 100 μM.