Accession Number : AD1030913


Title :   Development of Diazaquinomycin Class Antibiotics for the Treatment of Drug-Resistant TB Infections


Descriptive Note : Technical Report,15 Jul 2013,14 Jul 2016


Corporate Author : University of Illinois at Chicago Chicago United States


Personal Author(s) : Franzblau,Scott ; Klein,Larry


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1030913.pdf


Report Date : 01 Oct 2016


Pagination or Media Count : 64


Abstract : In the current proposal, we utilize a panel of TB tests to generate potential therapeutics that target M. tuberculosis growth. The source of therapeutics is our growing library of aquatic bacteria, since these unique microorganisms have the proven ability to produce unique molecules that have a relatively high potential for use as medicines. This model has been successful in just a few years of its implementation, as recently we have licensed a novel anti-TB natural product to B and C Biopharm in South Korea. In addition, from screening our library of compounds against non-replicating TB, we have identified eight aquatic bacterial strains that target non-replicating TB, all of which do not exhibit signs of known antibiotic classes. From this screening we have also identified a promising class of antibiotics (DAQ) that appear to selectively target mycobacteria with drug-like potency. In this proposal we will 1) identify the antibiotics from the eight actinomycete strains that target non-replicating M. tuberculosis and evaluate their ability to be viable TB leads, 2) synthesize and evaluate the DAQ antibiotics for their potential to become viable drugs, and 3) identify how the DAQ antibiotics work in the cell. The Partnering PI Option poises us to fuse small molecule chemistry, aquatic microbiology, and molecular biology with drug discovery to utilize novel small molecules that target NR M. tuberculosis. This proposal utilizes our capacity to identify antibiotics from libraries of aquatic actinomycete strains, and thoroughly profile hits and leads with respect to anti-TB potency, selectivity, and drug-like behavior.


Descriptors :   Antibiotics , Tuberculosis , therapeutics , infectious diseases , infection


Subject Categories : Pharmacology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE