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- Title
4-Hydroxy- α-Tetralone and its Derivative as Drug Resistance Reversal Agents in Multi Drug Resistant E scherichia coli.
- Authors
Dwivedi, Gaurav R.; Upadhyay, Harish C.; Yadav, Dharmendra K.; Singh, Vigyasa; Srivastava, Santosh K.; Khan, Feroz; Darmwal, Nandan S.; Darokar, Mahendra P.
- Abstract
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 ( yojI) 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.
- Subjects
DRUG resistance in microorganisms; TETRALONES; MULTIDRUG resistance; MICROBIAL viability counts; DIAGNOSTIC use of polymerase chain reaction; CARRIER proteins
- Publication
Chemical Biology & Drug Design, 2014, Vol 83, Issue 4, p482
- ISSN
1747-0277
- Publication type
Article
- DOI
10.1111/cbdd.12263