title: Synthesis, biological evaluation and computational studies of acrylohydrazide derivatives as potential Staphylococcus aureus NorA efflux pump inhibitors
creator: Kumar, Gautam
creator: Godavari, Ambati Goutami
creator: Tambat, Rushikesh
creator: Kumar, Siva
creator: Nandanwar, Hemraj
creator: Sobhia,  M. Elizabeth
creator: Jachak, Sanjay M
subject: QR180 Immunology
description: The NorA efflux pump decreases the intracellular concentration of fluoroquinolones (ciprofloxacin, norfloxacin) by effluxing them from Staphylococcus aureus cells. The synthesis of novel acrylohydrazide derivatives was achieved using well-known reactions and were characterized by various spectroscopy techniques. The synthe-sized 50 compounds were evaluated for the NorA efflux pump inhibition activity against S. aureus SA-1199B (norA++) and K1758 (norA-) strains. The study provided two most active compounds viz. 19 and 52. Compound 19 was found to be most active in potentiating effect of norfloxacin and also it showed enhanced uptake, efflux inhibition in ethidium bromide assay. Further compound 19 also enhanced post antibiotic effect and reduced mutation prevention concentration of norfloxacin. The homology modeling study was performed to elucidate three-dimensional structure of NorA. Docking studies of potent molecules were done to find the binding affinity and interaction with active site residues. Further, all the tested compounds exhibited good ADME and drug-likeness properties insilico. Based on the in-silico studies and detailed in vitro studies, acrylohydrazides derivatives may be considered as potential NorA EPI candidates.
publisher: Elsevier Science
date: 2020-11
type: Article
type: PeerReviewed
relation: https://linkinghub.elsevier.com/retrieve/pii/S0045-2068(20)31522-4
identifier:   Kumar, Gautam and Godavari, Ambati Goutami and Tambat, Rushikesh and Kumar, Siva and Nandanwar, Hemraj and Sobhia, M. Elizabeth and Jachak, Sanjay M  (2020) Synthesis, biological evaluation and computational studies of acrylohydrazide derivatives as potential Staphylococcus aureus NorA efflux pump inhibitors.  BIOORGANIC CHEMISTRY, 104.       
relation: http://crdd.osdd.net/open/2627/