Synthesis, Biological Evaluation and in Silico Study of N‐(2‐ and 3‐Pyridinyl)benzamide Derivatives as Quorum Sensing Inhibitors against Pseudomonas aeruginosa

Abstract

The effectiveness of treating bacterial infections is seriously threatened by the emergence of bacterial resistance to chemical treatment. Growth of microbes in biofilm is one of the main causes of resistance to antimicrobial drugs. Quorum sensing (QS) inhibition, which targets the QS signalling system by obstructing cellcell communication, was developed as an alternative treatment by creating innovative anti-biofilm drugs. Therefore, the goal of this study is to develop novel antimicrobial drugs that are effective against Pseudomonas aeruginosa by inhibiting QS and acting as anti-biofilm agents. In this study, N-(2-and 3-pyridinyl)benzamide derivatives were selected to design and syntheses. Antibiofilm activity was revealed by all the synthesized compounds and the biofilm was visibly impaired, and the OD 595nm readings of solubilized biofilm cells presented a momentous difference between the treated and untreated biofilms. The best anti-QS zone was observed for compound 5d and found to be 4.96 mm. Through in silico research, the physicochemical characteristics and binding manner of these produced compounds were examined. For the purpose of understanding the stability of the protein and ligand complex, molecular dynamic simulation was also carried out. The overall findings showed that N-(2-and 3-pyridinyl)benzamide derivatives could be the key to creating effective newer antiquorum sensing drugs that are effective against different bacteria.

Synthesis, in Silico Study and Biological Evaluation of N‐(Benzothiazol/Thiazol‐2‐yl)benzamide Derivatives as Quorum Sensing Inhibitors against Pseudomonas aeruginosa

“…2‐Aminobenzothiazole benzamide derivatives were made using a modified version of described approach [37] . At room temperature, 2‐amino benzothiazole (1.0 equiv) was combined with the appropriate acid (1.0 equiv), EDC.HCl (1.1 equiv), DMAP (1.1 equiv), and DCM as a solvent.…”

“…Chemistry 2-Aminobenzothiazole benzamide derivatives were made using a modified version of described approach. [37] At room temperature, 2-amino benzothiazole (1.0 equiv) was combined with the appropriate acid (1.0 equiv), EDC.HCl (1.1 equiv), DMAP (1.1 equiv), and DCM as a solvent. In order to produce the relevant benzamide derivatives (3 a-h), the reaction mixture was stirred at ambient temperature for 12 h (Scheme 1).…”

“…[18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] Our research group is also involved in developing new quorum sensing inhibitors. [37] Most quorum sensing inhibitors that were developed either lost their effectiveness or become resistant to pathogenicity. Therefore, it's important to develop novel, more effective quorum sensing inhibitors.…”

“…Several publications described synthetic quorum sensing inhibitors [18–36] . Our research group is also involved in developing new quorum sensing inhibitors [37] . Most quorum sensing inhibitors that were developed either lost their effectiveness or become resistant to pathogenicity.…”