title: Gallic acid-based indanone derivative interacts synergistically with tetracycline by inhibiting efflux pump in multidrug resistant E. coli.
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.
authors.affiliation: Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Near Kukrail Picnic Spot, P.O. CIMAP, Lucknow, 226015, India.|School of Environmental Science, Babasaheb Bhim Rao Ambedkar University, Lucknow, 226025, UP, India.
authors.forename: Gaurav Raj
authors.initials: GR
authors.lastname: Dwivedi
authors.affiliation: Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Near Kukrail Picnic Spot, P.O. CIMAP, Lucknow, 226015, India.
authors.forename: Nimisha
authors.initials: N
authors.lastname: Tiwari
authors.affiliation: Chemical Sciences Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Near Kukrail Picnic Spot, P.O. CIMAP, Lucknow, 226015, India.
authors.forename: Aastha
authors.initials: A
authors.lastname: Singh
authors.affiliation: Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Near Kukrail Picnic Spot, P.O. CIMAP, Lucknow, 226015, India.
authors.forename: Akhil
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Near Kukrail Picnic Spot, P.O. CIMAP, Lucknow, 226015, India.|Department of Biomedical Engineering, Faculty of Electronics and Communication, Brno University of Technology, Antonínská 548/1, 60190, Brno, Czech Republic.
authors.forename: Sudeep
authors.initials: S
authors.lastname: Roy
authors.affiliation: Chemical Sciences Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Near Kukrail Picnic Spot, P.O. CIMAP, Lucknow, 226015, India. as.negi@cimap.res.in.
authors.forename: Arvind Singh
authors.initials: AS
authors.lastname: Negi
authors.affiliation: Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Near Kukrail Picnic Spot, P.O. CIMAP, Lucknow, 226015, India.
authors.forename: Anirban
authors.initials: A
authors.lastname: Pal
authors.affiliation: Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Near Kukrail Picnic Spot, P.O. CIMAP, Lucknow, 226015, India.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Chanda
authors.affiliation: Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Near Kukrail Picnic Spot, P.O. CIMAP, Lucknow, 226015, India.
authors.forename: Ashok
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Near Kukrail Picnic Spot, P.O. CIMAP, Lucknow, 226015, India. mp.darokar@cimap.res.in.
authors.forename: Mahendra P
authors.initials: MP
authors.lastname: Darokar
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004357:Drug Synergism; D064420:Drug-Related Side Effects and Adverse Reactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects*; D005707:Gallic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D007189:Indans / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D012772:Shock, Septic / Q000517:prevention & control; D013752:Tetracycline / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D007189:Indans; D005707:Gallic Acid; C013352:indacrinone; D013752:Tetracycline
keywords: ATPase; Efflux pump inhibition; Gallic acid; Indanone derivative; Subacute oral toxicity; Synergy