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allied
academies
September 20-21, 2017 | Philadelphia, USA
Global summit on
TUBERCULOSIS AND LUNG DISEASE
Int J Respir Med 2017 Volume 2 Issue 2
I
n the present study, we attempted to develop novel Mycobacterium tuberculosis
(Mtb) inhibitors by exploring the pharmaceutically underexploited enzyme targets
which are majorly involved in cell wall biosynthesis of mycobacteria. For this purpose
glutamate racemase (coded by MurI 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. Forty eight 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. Few compounds have
shown IC50 of 4-5μM which are remarkable and were found to be non-cytotoxic.
Molecular dynamics, dormant models and cardiotoxicity studies of the most active
molecules are in process.
e:
santhireddy90@gmail.comDesign and identification of
Mycobacterium tuberculosis
Glutamate racemase (MurI) inhibitors
Prasanthi Malapati
BITS-Pilani Hyderabad, India