What is it about?
There is positive news in the antibacterial world. A convenient synthesis of new fluoroquinolone molecules substituted with endo-nortropine, a natural alkaloid, has been described. All the twelve molecules were evaluated for their antibacterial activity. Among these, two required only nano molar quantities to kill bacteria that cause cholera and post surgery wound infections. One of these two molecules, designated as RG, was chiral and required only half the quantity to kill cholera causing pathogen as compared to normally used drug, levofloxacin. In case of the bacteria that causes post surgery wound infections and many others, this molecule (RG) was required only in one tenth the quantity as compared to levofloxacin. Computational studies done with RG molecule for infection causing bacterial enzyme, called DNA gyrase, predicted increased interactions for the molecule as compared to standard antibacterial levofloxacin. A humble beginning, but still a long way to go for development into prescribed drug.
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Why is it important?
Bacteria responsible for cholera and post surgery wound infections are one of the dreaded organisms on this earth. This is evident from the fact that cholera has become endemic at places that had been free of its effect for centuries as reported in 2015 by an article in PLOS Pathogens. Similarly, according to WHO, 15 to 25 lakh patients are affected by post surgery wound infections each year in low and middle income group countries. Evolutionary reasons and unnecessary use of antibiotics has rendered effective drugs like penicillin and many fluoroquinolones as ineffective. Further, emergence of resistant strains against drugs of last resort like methicillin and vancomycin is misfortune of the present world and has necessitated the need to design and discover new, efficient and cost effective molecules for the combat. The molecules reported in this article have been synthesized by manipulating present day fluoroquinolone drug levofloxacin. This class of molecules are cost effective to synthesize, excellently bio available, have good solubility and prolonged serum half-life. They can be administered both by oral and parenteral routes.
Perspectives
Fluoroquinolones are very competitive molecules with many of them already in market and a lot more reported. When Ram, 1st author of the article, approached me with an idea of exploring their medicinal chemistry as a part of his PhD work, I was a bit reluctant. But a determined student started a systematic literature survey and was able to locate some gaps. There was only one report of 1991 in JMC having nitrogen containing bridged bicyclic molecules decorated at C-7 position. This paved the way to initiate this work and collaboration with a reputed national laboratory and industry. I am thankful to all the collaborators who contributed in their own way to this work. Dr. Bansal, from industry, rendered his industrial facilities available while Dr. Pinnaka and Ms. Sidhu took up the biological activity evaluations. Mr. Ashok helped Mr. Ramkrushna A. Salunke with computational calculations to predict the mechanism of inhibiting the DNA gyrase enzyme that RG molecule inhibits.
Dr Manmohan Chhibber
Thapar Institute of Engineering and Technology (TIET), Patiala, India
Read the Original
This page is a summary of: Enhanced Antibacterial Activity of Endo-nortropine Substituted (C-7) Fluoroquinolones Against V. cholerae, S. aureus and B. subtilis, Letters in Drug Design & Discovery, June 2018, Bentham Science Publishers,
DOI: 10.2174/1570180814666171026162304.
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