Antibacterial and Synergy of Clavine Alkaloid Lysergol and its Derivatives Against Nalidixic Acid‐Resistant Escherichia coli. (21st March 2013)

• Record Type: Journal Article
• Authors: Maurya, Anupam; Dwivedi, Gaurav R.; Darokar, Mahendra P.; Srivastava, Santosh K.
• Is Part Of: Chemical biology & drug design. Volume 81:Number 4(2013:Apr.)
• Page Start: 484
• Page End: 490
• Publication Date: 2013-03-21
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12103
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" xml:lang="en" id="cbdd12103-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Antibacterial activity of lysergol (<bold>1</bold>) and its semi‐synthetic derivatives (<bold>2–14</bold>) and their synergy with the conventional antibiotic nalidixic acid (NA) against nalidixic acid‐sensitive (NASEC) and nalidixic acid‐resistant (NAREC) strains of <italic>Escherichia coli</italic> were evaluated. Lysergol (<bold>1</bold>) and derivatives (<bold>2</bold>–<bold>14</bold>) 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 (<bold>1</bold>) and its derivatives <bold>10</bold> and <bold>11</bold> brought down eightfold reductions in the MIC of tetracycline (TET) against multidrug‐resistant clinical isolate of <italic>E. coli</italic> (MDREC). Treatment of these strains with the combinations of antibiotics and lysergol and its derivatives <bold>10</bold> and <bold>11</bold> (at reduced concentrations) significantly decreased the viability of cells. In an another observation, lysergol and its derivatives <bold>10</bold> and <bold>11</bold> 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.</p> </abstract>