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 |
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Hauptverfasser: | , , , , , , , |
Format: | Artikel |
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. |
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ISSN: | 1747-0277 1747-0285 |
DOI: | 10.1111/cbdd.12263 |