Premium
Antibacterial and Synergy of Clavine Alkaloid Lysergol and its Derivatives Against Nalidixic Acid‐Resistant E scherichia coli
Author(s) -
Maurya Anupam,
Dwivedi Gaurav R.,
Darokar Mahendra P.,
Srivastava Santosh K.
Publication year - 2013
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12103
Subject(s) - nalidixic acid , escherichia coli , tetracycline , efflux , antibacterial activity , minimum inhibitory concentration , multiple drug resistance , chemistry , antibiotics , microbiology and biotechnology , bacteria , biochemistry , biology , gene , genetics
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 E scherichia 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 ATP ase 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.