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Volume 5, Issue 3 (Suppl)
J Infect Dis Ther, an open access journal
ISSN:2332-0877
Infectious Diseases 2017
August 21-23, 2017
3
rd
Annual Congress on
Infectious Diseases
August 21-23, 2017 San Francisco, USA
Design and identification of Mycobacterium tuberculosis glutamate racemase (MurI) inhibitors
Prasanthi Malapati
and
Dharmarajan Sriram
Birla Institute of Technology and Science, India
I
n the present study, we attempted to develop novel Mycobacterium tuberculosis (Mtb) inhibitors by exploring the
pharmaceutically underexploited enzyme targets which aremajorly involved in cell wall biosynthesis of mycobacteria. For this
purpose glutamate racemase (coded by Murl gene) was selected. This enzyme is able to construct these cell walls by synthesizing
D-glutamate from L-glutamate through racemization. Furthermore enzyme is not expressed nor its product, D-glutamate is
normally found in mammals, and hence inhibiting this enzyme should not result in toxicity to the mammalian host organism.
A library of BITS in house compounds were screened against Mtb MurI enzyme using glide module in Schrodinger software.
Based on docking scores, interactions and synthetic feasibility one of the hit lead was identified, further optimization of lead
was attempted and its derivatives were synthesized. 48 derivatives of 2-phenylbenzo[d]oxazole and 2-phenylbenzo[d]thiazole
were synthesized and evaluated for Mtb MurI inhibition study, in vitro activities against Mtb, cytotoxicity against RAW 264.7
cell line Mtb. Few compounds have shown IC50 of 4-5µMwhich are remarkable and were found to be non-cytotoxic. Molecular
dynamics, dormant models and cardiotoxicity studies of the most active molecules are in process.
santhireddy90@gmail.comJ Infect Dis Ther 2017, 5:3 (Suppl)
DOI: 10.4172/2332-0877-C1-027