title: Antibacterial and synergy of clavine alkaloid lysergol and its derivatives against nalidixic acid-resistant Escherichia coli.
abstract: Antibacterial activity of lysergol (1) and its semi-synthetic derivatives (2-14) and their synergy with the conventional antibiotic nalidixic acid (NA) against nalidixic acid-sensitive (NASEC) and nalidixic acid-resistant (NAREC) strains of Escherichia coli were evaluated. Lysergol (1) and derivatives (2-14) did not possess antibacterial activity of their own, but in combination, they significantly reduced the minimum inhibitory concentration (MIC) of NA. All the derivatives showed two- to eightfold reduction in the MIC of NA against NAREC and NASEC. Further, lysergol (1) and its derivatives 10 and 11 brought down eightfold reductions in the MIC of tetracycline (TET) against multidrug-resistant clinical isolate of E. coli (MDREC). Treatment of these strains with the combinations of antibiotics and lysergol and its derivatives 10 and 11 (at reduced concentrations) significantly decreased the viability of cells. In an another observation, lysergol and its derivatives 10 and 11 inhibited ATP-dependent efflux pumps, which was evident by ATPase inhibition and down-regulation of multidrug ABC transporter ATP-binding protein (yojI) gene. These results may be of great help in antibacterial drug development from a very common, inexpensive, and non-toxic natural product.
authors.affiliation: Department of Medicinal Chemistry, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, India.
authors.forename: Anupam
authors.initials: A
authors.lastname: Maurya
authors.forename: Gaurav R
authors.initials: GR
authors.lastname: Dwivedi
authors.forename: Mahendra P
authors.initials: MP
authors.lastname: Darokar
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Srivastava
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004357:Drug Synergism; D004873:Ergolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004876:Ergot Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects*; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D009268:Nalidixic Acid / Q000494:pharmacology*; D013752:Tetracycline / Q000494:pharmacology
chemical_list: D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D004873:Ergolines; D004876:Ergot Alkaloids; D029968:Escherichia coli Proteins; D009268:Nalidixic Acid; D000251:Adenosine Triphosphatases; D013752:Tetracycline; C061884:lysergol