4‐Hydroxy‐ α ‐Tetralone and its Derivative as Drug Resistance Reversal Agents in Multi Drug Resistant E scherichia coli

The purpose of present investigation was to understand the drug resistance reversal mechanism of 4‐hydroxy‐ α ‐tetralone ( 1 ) isolated from Ammannia spp. along with its semi‐synthetic derivatives ( 1a – 1e ) using multidrug resistant Escherichia coli ( MDREC ). The test compounds did not show signi...

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Veröffentlicht in:Chemical biology & drug design 2014-04, Vol.83 (4), p.482-492
Hauptverfasser: Dwivedi, Gaurav R., Upadhyay, Harish C., Yadav, Dharmendra K., Singh, Vigyasa, Srivastava, Santosh K., Khan, Feroz, Darmwal, Nandan S., Darokar, Mahendra P.
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Sprache:eng
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Zusammenfassung:The purpose of present investigation was to understand the drug resistance reversal mechanism of 4‐hydroxy‐ α ‐tetralone ( 1 ) isolated from Ammannia spp. along with its semi‐synthetic derivatives ( 1a – 1e ) using multidrug resistant Escherichia coli ( MDREC ). The test compounds did not show significant antibacterial activity of their own, but in combination, they reduced the minimum inhibitory concentration ( MIC ) of tetracycline ( TET ). In time kill assay, compound 1 and its derivative 1e in combination with TET reduced the cell viability in concentration dependent manner. Compounds 1 and 1e were also able to reduce the mutation prevention concentration of TET . Both compounds showed inhibition of ATP dependent efflux pumps. In real time polymerase chain reaction ( RT ‐ PCR ) study, compounds 1 and 1e alone and in combination with TET showed significant down expression of efflux pump gene ( yoj I) encoding multidrug ATP binding cassettes ( ABC ) transporter protein. Molecular mechanism was also supported by the in silico docking studies, which revealed significant binding affinity of compounds 1 and 1e with YojI. This study confirms that compound 1 and its derivative 1e are ABC efflux pump inhibitors which may be the basis for development of antibacterial combinations for the management of MDR infections from inexpensive natural product.
ISSN:1747-0277
1747-0285
DOI:10.1111/cbdd.12263