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Published on: April 18, 2019
Gallic acid-based indanone derivative interacts synergistically with tetracycline by inhibiting efflux pump in
Gaurav Raj Dwivedi1,2, Nimisha Tiwari1, Aastha Singh3
1Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Near Kukrail Picnic Spot, P.O. CIMAP, Lucknow, 226015, India.
Abstract:
The purpose of the present study was to study the synergy potential of gallic acid-based derivatives in combination with conventional antibiotics using multidrug resistant cultures of Escherichia coli. Gallic acid-based derivatives significantly reduced the MIC of tetracycline against multidrug resistant clinical isolate of E. coli. The best representative, 3-(3',4,'5'-trimethoxyphenyl)-4,5,6-trimethoxyindanone-1, an indanone derivative of gallic acid, was observed to inhibit ethidium bromide efflux and ATPase which was also supported by in silico docking. This derivative extended the post-antibiotic effect and decreased the mutation prevention concentration of tetracycline. This derivative in combination with TET was able to reduce the concentration of TNFα up to 18-fold in Swiss albino mice. This derivative was nontoxic and well tolerated up to 300 mg/kg dose in subacute oral toxicity study in mice. This is the first report of gallic acid-based indanone derivative as drug resistance reversal agent acting through ATP-dependent efflux pump inhibition.
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