title: NorA efflux pump inhibitory activity of coumarins from Mesua ferrea.
abstract: The purpose of this investigation was to study the modulator and efflux pump inhibitor activity of coumarins isolated from Mesua ferrea against clinical strains as well as NorA-over expressed strain of Staphylococcus aureus 1199B. Seven coumarins were tested for modulator activity using ethidium bromide (EtBr) as a substrate. Compounds 1, 4-7 modulated the MIC of EtBr by ≥ 2 fold against wild type clinical strains of S. aureus 1199 and S. aureus 1199B, whereas compounds 4-7 modulated the MIC of EtBr by ≥ 16 fold against MRSA 831. Compounds 1, 4-7 also reduced the MIC of norfloxacin by ≥ 8 fold against S. aureus 1199B, and 4-6 reduced the MIC of norfloxacin by ≥ 8 fold against MRSA 831 at half of their MICs. Inhibition of EtBr efflux by NorA-overproducing S. aureus 1199B and MRSA 831 confirmed the role of compounds 4-6 as NorA efflux pump inhibitors (EPI). Dose-dependent activity at sub-inhibitory concentration (6.25 μg/mL) suggested that compounds 4 and 5 are promising EPI compared to verapamil against 1199B and MRSA 831 strains.
authors.affiliation: Department of Natural Products, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar-160062, Punjab, India.
authors.forename: Somendu K
authors.initials: SK
authors.lastname: Roy
authors.forename: Neela
authors.initials: N
authors.lastname: Kumari
authors.forename: Sonika
authors.initials: S
authors.lastname: Pahwa
authors.forename: Udai C
authors.initials: UC
authors.lastname: Agrahari
authors.forename: Kamlesh K
authors.initials: KK
authors.lastname: Bhutani
authors.forename: Sanjay M
authors.initials: SM
authors.lastname: Jachak
authors.forename: Hemraj
authors.initials: H
authors.lastname: Nandanwar
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D028084:Clusiaceae / Q000737:chemistry*; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors*; D009643:Norfloxacin / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003374:Coumarins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009643:Norfloxacin; D010936:Plant Extracts; C075040:NorA protein, Staphylococcus
keywords: Clinical strain; Coumarins; Mesua ferrea; NorA-pump inhibitor; Staphylococcus aureus