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Discovery of novel dihydronaphthalene -imidazole ligands as potential inhibitors of Staphylococcus aureus multidrug resistant NorA efflux pump: A combination of experimental and in silico molecular docking studies

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Discovery of novel dihydronaphthalene -imidazole ligands as potential inhibitors of Staphylococcus aureus multidrug resistant NorA efflux pump: A combination of experimental and in silico molecular docking studies
 
Creator Malik, Asif A.
Dangroo, Nisar A.
Kaur, Parminder
Attery, Shobit
Rather, Manzoor A.
Khan, Abrar
Ara, Tabassum
Nandanwar, Hemraj
 
Subject QR Microbiology
 
Description Overexpression of the efflux pump is a predominant mechanism by which bacteria show antimicrobial resistance (AMR) and leads to the global emergence of multidrug resistance (MDR). In this work, the inhibitory potential of library of dihydronapthyl scaffold-based imidazole derivatives having structural resemblances with some known efflux pump inhibitors (EPI) were designed, synthesized and evaluated against efflux pump inhibitor against overexpressing bacterial strains to study the synergistic effect of compounds and antibiotics. Out of 15 compounds, four compounds (Dz-1, Dz-3, Dz-7, and Dz-8) were found to be highly active. DZ-3 modulated the MIC of ciprofloxacin, erythromycin, and tetracycline by 128-fold each against 1199B, XU212 and RN4220 strains of S. aureus respectively. DZ-3 also potentiated tetracycline by 64-fold in E. coli AG100 strain. DZ-7 modulated the MIC of both tetracycline and erythromycin 128-fold each in S. aureus XU212 and S. aureus RN4220 strains. DZ-1 and DZ-8 showed the moderate reduction in MIC of tetracycline in E. coli AG100 only by 16-fold and 8-fold, respectively. DZ-3 was found to be the potential inhibitor of NorA as determined by ethidium bromide efflux inhibition and accumulation studies employing NorA overexpressing strain SA-1199B. DZ-3 displayed EPI activity at non-cytotoxic concentration to human cells and did not possess any antibacterial activity. Furthermore, molecular docking studies of DZ-3 was carried out in order to understand the possible binding sites of DZ-3 with the active site of the protein. These studies indicate that dihydronaphthalene scaffolds could serve as valuable cores for the development of promising EPIs.
 
Publisher ELSEVIER
 
Date 2024-05
 
Type Article
PeerReviewed
 
Relation https://sciencedirect.com/science/article/abs/pii/S0882401024000949?via%3Dihub
http://crdd.osdd.net/open/3126/
 
Identifier Malik, Asif A. and Dangroo, Nisar A. and Kaur, Parminder and Attery, Shobit and Rather, Manzoor A. and Khan, Abrar and Ara, Tabassum and Nandanwar, Hemraj (2024) Discovery of novel dihydronaphthalene -imidazole ligands as potential inhibitors of Staphylococcus aureus multidrug resistant NorA efflux pump: A combination of experimental and in silico molecular docking studies. MICROBIAL PATHOGENESIS, 190.