Design, Synthesis and Biological Evaluation of Triazole‐Containing 2‐Phenylindole and Salicylic Acid as Quorum Sensing Inhibitors Against Pseudomonas aeruginosa. Issue 32 (24th August 2018)

• Record Type: Journal Article
• Authors: Srinivasarao, Singireddi; Nizalapur, Shashidhar; Yu, Tsz Tin; Wenholz, Daniel Stanley; Trivedi, Prakruti; Ghosh, Balaram; Rangan, Krishnan; Kumar, Naresh; Gowri Chandra Sekhar, Kondapalli Venkata
• Is Part Of: ChemistrySelect. Volume 3:Issue 32(2018)
• Page Start: 9170
• Page End: 9180
• Publication Date: 2018-08-24
• Subjects: P. aeruginosa -- 2-phenyl indole -- Quorum sensing -- Salicylic acid -- Triazole; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201801622
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: 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. Abstract : In this work, we designed 2‐phenylindole‐amide‐triazole and salicyclic acid‐triazole analogues and synthesized thirty‐six compounds and screened for the QSI activity. Three compounds (from Series‐II)10 j, 11 b and11 e exhibited significant QSI activity with 60.82, 58.89 and 54.34% against P. aeruginosa MH602 at 250 μM respectively. These compounds were not found to be toxic in normal human embryonic kidney cell line (HEK 293).