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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, synthesis,
in vitro
antimycobacterial screening andmoleculardocking studies of novel benzimidazolyl
hydrazides
Kuppuswamy Umaa
PSG College of Pharmacy, India
Statement of Problem:
The emergence of severe mutated drug resistant strains of
Mycobacterium
has reinvigorated the
development of effective chemotherapy for efficient treatment of tuberculosis. Consequently, we have developed novel
benzimidazole derivatives and screened them for their antimycobacterial activity along with silico studies with a validated
target enzyme Enoyl-acyl-carrier reductase (Inh A).
Methodology:
A series of N', N''-[1-(1H-benzimidazole-2-yl)-2-(4-substituted phenyl ethane-1, 2-diyl)] substituted aromatic
hydrazide derivatives which were synthesized by condensation of o-phenylene diamine with organic acids, followed by Claisen-
Schmidt reaction and then subjected to bromination and finally treated with a strong nucleophile. Structures were elucidated
with spectral data and subjected to antimycobacterial screening by two models, the Alamar Blue assay and Luciferase reporter
phage assay. The inhibitory concentrations and the percentage reduction in relative light units were assessed respectively to
evaluate the
in vivo
efficacy of the novel compounds. Molecular docking studies with the enoyl acyl carrier protein reductase
(InhA) of
M. tuberculosis
were performed to check for binding profiles of these compounds.
Findings:
Four compounds showed significant activity with IC values of 0.5 mg/ml in Alamar Blue assay and greater than 90%
reduction in relative light units at both 50 and 100 μgm/ml levels. Among the four, N’, N”-[1-(1H-benzimidazol-2-yl)-2-(4-
chlorophenyl) ethane-1, 2-diyl] di isonicotino hydrazide was found to be the most active (
~
98.3%) in this series, based on the
percentage reduction in relative light units. In order to rationalize the biological results of our compounds, molecular docking
studies with the enoyl acyl carrier protein reductase (InhA) of
M. tuberculosis
were performed. The above compounds showed
good H-bond interactions with Gly-96, exhibiting a good dock score and fitted well in the binding pocket of Inh A.
Conclusion:
The compounds that exhibit promising activity profile against
Mycobacterium
tuberculosis H
37
Rv strain with
significant docking scores could become excellent molecules for developing more potent antimycobacterial agents.
umaagangadhararao@gmail.comJ Infect Dis Ther 2017, 5:3 (Suppl)
DOI: 10.4172/2332-0877-C1-027