Abstract: A series of 1-(1H-benzimidazol-2-yl)-3-(substituted phenyl)-2-propen-1-one were allowed to react with hydrazine hydrate and phenyl hydrazine in submitted reactions to get pyrazoline and phenyl pyrazoline derivatives. All the compounds entered for screening at the Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv strain (ATCC 27294) using Microplate Alamar Blue Assay (MABA) susceptibility test. The results expressed as MIC (minimum inhibitory concentration) in μg/mL. Among the fifteen compounds, eight compounds were found to have MIC values less than 10 μg/mL. These were subjected for cytotoxicity assay in VERO cells to determine CC50 (cytotoxic concentration 50%) values and finally SI (Selectivity Index) were calculated. Compound (XV) 2-[5-(4- fluorophenyl)-1-phenyl-4,5-dihydro-1H-3-pyrazolyl]-1Hbenzimidazole was considered the best candidate of the series that could be a good starting point to develop new lead compounds in the fight against tuberculosis.
Abstract: There is an urgent need to develop novel
Mycobacterium tuberculosis (Mtb) drugs that are active against drug
resistant bacteria but, more importantly, kill persistent bacteria. Our
study structured based on integrated analysis of metabolic pathways,
small molecule screening and similarity Search in PubChem
Database. Metabolic analysis approaches based on Unified weighted
used for potent target selection. Our results suggest that pantothenate
synthetase (panC) and and 3-methyl-2-oxobutanoate hydroxymethyl
transferase (panB) as a appropriate drug targets. In our study, we
used pantothenate synthetase because of existence inhibitors. We
have reported the discovery of new antitubercular compounds
through ligand based approaches using computational tools.
Abstract: Aptamers are useful tools in microorganism
researches, diagnoses, and treatment. Aptamers are specific target
molecules formed by oligonucleic acid molecules, and are not
decomposed by alcohol. Aptamers used to detect Mycobacterium
tuberculosis (MTB) have been proved to have specific affinity to the
outer membrane proteins of MTB. This article presents a biosensor
chip set with aptamers for early detection of MTB with high specificity
and sensitivity, even in very low concentration. Meanwhile, we have
already made a modified hydrophobic facial mask module with
internal rendering hydrophobic for effectively collecting M.
tuberculosis.
Abstract: Sputum smear conversion after one month of antituberculosis
therapy in new smear positive pulmonary tuberculosis
patients (PTB+) is a vital indicator towards treatment success. The
objective of this study is to determine the rate of sputum smear
conversion in new PTB+ patients after one month under treatment of
National Institute of Diseases of the Chest and Hospital (NIDCH).
Analysis of sputum smear conversion was done by re-clinical
examination with sputum smear microscopic test after one month.
Socio-demographic and hematological parameters were evaluated to
perceive the correlation with the disease status. Among all enrolled
patients only 33.33% were available for follow up diagnosis and of
them only 42.86% patients turned to smear negative. Probably this
consequence is due to non-coherence to the proper disease
management. 66.67% and 78.78% patients reported low haemoglobin
and packed cell volume level respectively whereas 80% and 93.33%
patients accounted accelerated platelet count and erythrocyte
sedimentation rate correspondingly.
Abstract: An alarming emergence of multidrug-resistant strains
of the tuberculosis pathogen Mycobacterium tuberculosis and
continuing high worldwide incidence of tuberculosis has invigorated
the search for novel drug targets. The enzyme glutamate racemase
(MurI) in bacteria catalyzes the stereoconversion of L-glutamate to
D-glutamate which is a component of the peptidoglycan cell wall of
the bacterium. The inhibitors targeted against MurI from several
bacterial species have been patented and are advocated as promising
antibacterial agents. However there are none available against MurI
from Mycobacterium tuberculosis, due to the lack of its threedimensional
structure. This work accomplished two major objectives.
First, the tertiary structure of MtMurI was deduced computationally
through homology modeling using the templates from bacterial
homologues. It is speculated that like in other Gram-positive bacteria,
MtMurI exists as a dimer and many of the protein interactions at the
dimer interface are also conserved. Second, potent candidate
inhibitors against MtMurI were identified through docking against
already known inhibitors in other organisms.