Design,synthesis, biological evaluation and in silico studies of N-(pyridin-2-yl)-benzamides derivatives as quorum sensing inhibitors |
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| Institution: | 1. University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India;2. Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (B.H.U.), Varanasi, 221005, U.P, India;3. Department of Biophysics, Panjab University, Chandigarh, 160014, India;1. ?stanbul University- Cerrahpa?a, Faculty of Engineering, Department of Chemistry, ?stanbul, Turkey;2. Atatürk University, Faculty of Science, Department of Chemistry, Erzurum, Turkey;3. Biruni University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Istanbul, Turkey;4. Tekirda? Nam?k Kemal University, Faculty of Arts and Sciences, Department of Chemistry, Tekirda?, Turkey;1. Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands;2. State Key Laboratory of Crop Stress Biology for Arid Areas, Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F University, Yangling 712100, Shaanxi, China;3. Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, the Netherlands;4. Department of Cell Biology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands;5. Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, China;6. Department of Hospital Pharmacy, Erasmus MC-University Medical Center, Rotterdam, the Netherlands;7. Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7028 Trondheim, Norway;8. Institute of Technology, University of Tartu, 50090 Tartu, Estonia;1. University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India;2. Texas Tech University Health Sciences Center, Ophthalmology Dept Lbk Genl, Lubbock, Texas, USA, 3601 4th Street, Lubbock TX 79430, United States;3. Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Shoolini University, Solan-173229, Himachal Pradesh, India;4. Department of Biophysics, Panjab University, Chandigarh 160014, India;1. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt;2. Medicinal Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt;1. School of Medicine, University of Virginia, Charlottesville, VA, USA;2. Department of Obstetrics and Gynecology, University of Virginia, Charlottesville, VA, USA |
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| Abstract: | The emergence of bacterial resistance against chemical treatment is a big threat to the efficacy of bacterial infection treatment. One of the major reasons for resistance to antimicrobial agents is growth of microorganisms in biofilm. An alternative treatment by developing novel anti-biofilm agents had led to the concept of quorum sensing (QS) inhibition, which primarily targets QS signaling system by disrupting cell-cell communication. Therefore, this study focuses to develop novel antimicrobial agents which work by QS inhibition and act as anti-biofilm agents against Bacillus Subtilis and Pseudomonas Aeruginosa. In this work, a natural product-like scaffolds from Asinex library were screened and N-pyridin-2-yl-benzamide moiety was chosen to design and synthesize. Synthesized compounds were evaluated for potential anti-biofilm activity for the aforesaid microorganisms and also checked for cell viability assay, where two potent compounds 3a and 3c showed their static biofilm activity to ～59% and ～58% at 100 μM, respectively against Bacillus subtilis. These synthesized compounds were investigated for physicochemical parameters and binding mode prediction through molecular modelling tools. The interactions and stability of these compounds showed better affinity towards TasA and LasR proteins from Bacillus subtilis and Pseudomonas aeruginosa, respectively. Furthermore, molecular dynamic simulation for 100 ns was executed in order to appreciate the stability of the protein and ligand complex. The overall results promised that N-pyridin-2-yl-benzamide derivatives can be discovered as a lead in developing potent anti-quorum sensing agents against various bacteria. |
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| Keywords: | Synthesis Biological evaluation Quorum sensing Quorum sensing inhibitors |
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