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: Studies were carried out to determine the in vitro
susceptibility of the typhoid pathogens to combined action of Euphorbia hirta, Euphorbia heterophylla and Phyllanthus niruri. Clinical isolates of the typhoid bacilli were subjected to susceptibility testing using agar diffusion technique and the minimum inhibitory
concentration (MIC) determined with tube dilution technique. These
isolates, when challenged with doses of the extracts from the three
medicinal plants showed zones of inhibition as wide as 26±0.2mm, 22±0.1mm and 18±0.0mm respectively. The minimum inhibitory concentration (MIC) revealed organisms inhibited at varying
concentrations of extracts: E. hirta (S. typhi 0.250mg/ml, S. paratyphi A 0.125mg/ml, S. paratyphi B 0.185mg/ml and S. paratyphi C 0.225mg/ml), E. heterophylla (S. typhi 0.280mg/ml, S. paratyphi A
0.150mg/ml, S. paratyphi B 0.200mg/ml and S. paratyphi C 0.250mg/ml) and P. niruri (S. typhi 0.150mg/ml, S. paratyphi A 0.100mg/ml, S. paratyphi B 0.115mg/ml and S. paratyphi C 0.125mg/ml). The results of the synergy between the three plants in
the ration of 1:1:1 showed very low MICs for the test pathogens as follows S. typhi 0.025mg/ml, S. paratyphi A 0.080mg/ml, S. paratyphi B 0.015mg/ml and S. paratyphi C 0.10mg/ml with the
diameter zone of inhibition (DZI) ranging from 35±0.2mm,
28±0.4mm, 20±0.1mm and 32±0.3mm respectively. The secondary
metabolites were identified using simple methods and HPLC. Organic components such as anthroquinones, different alkaloids,
tannins, 6-ethoxy-1,2,3,4-tetrahydro-2,2,4-trimethyl and steroids were identified. The prevalence of Salmonellae, a deadly infectious disease, is still very high in parts of Nigeria. The synergistic action of these three plants is very high. It is concluded that pharmaceutical companies should take advantage of these findings to develop new
anti-typhoid drugs from these plants.
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.
Abstract: The assessment of surface waters in Enugu metropolis
for fecal coliform bacteria was undertaken. Enugu urban was divided
into three areas (A1, A2 and A3), and fecal coliform bacteria
analysed in the surface waters found in these areas for four years
(2005-2008). The plate count method was used for the analyses. Data
generated were subjected to statistical tests involving; Normality test,
Homogeneity of variance test, correlation test, and tolerance limit
test. The influence of seasonality and pollution trends were
investigated using time series plots. Results from the tolerance limit
test at 95% coverage with 95% confidence, and with respect to EU
maximum permissible concentration show that the three areas suffer
from fecal coliform pollution. To this end, remediation procedure
involving the use of saw-dust extracts from three woods namely;
Chlorophora-Excelsa (C-Excelsa),Khayan-Senegalensis,(CSenegalensis)
and Erythrophylum-Ivorensis (E-Ivorensis) in
controlling the coliforms was studied. Results show that mixture of
the acetone extracts of the woods show the most effective
antibacterial inhibitory activities (26.00mm zone of inhibition)
against E-coli. Methanol extract mixture of the three woods gave best
inhibitory activity (26.00mm zone of inhibition) against S-areus, and
25.00mm zones of inhibition against E-Aerogenes. The aqueous
extracts mixture gave acceptable zones of inhibitions against the
three bacteria organisms.
Abstract: Today, cancer remains one of the major diseases that
lead to death. The main obstacle in chemotherapy as a main cancer
treatment is the toxicity to normal cells due to Multidrug Resistance
(MDR) after the use of anticancer drugs. Proposed solution to
overcome this problem is the use of MDR efflux inhibitor of cinchona
alkaloids which is delivered together with anticancer drugs
encapsulated in the form of polymeric nanoparticles. The particles
were prepared by the hydration method. The characterization of
nanoparticles was particle size, zeta potential, entrapment efficiency
and in vitro drug release. Combination nanoparticle size ranged 29-45
nm with a neutral surface charge. Entrapment efficiency was above
87% for the use quinine, quinidine or cinchonidine in combination
with etoposide. The release test results exhibited that the cinchona
alkaloids release released faster than that of etoposide. Collectively,
cinchona alkaloids can be packaged along with etoposide in
nanomicelles for better cancer therapy.
Abstract: Biologically active peptides are of particular interest
in food science and human nutrition because they have been shown to play several physiological roles. In vitro gastrointestinal digestion of lentil and whey proteins in this study produced high angiotensin-I converting enzyme inhibitory activity with 75.5±1.9 and 91.4±2.3%
inhibition, respectively. High ACE inhibitory activity was observed in lentil after 5 days of germination (84.3±1.2%). Fractionation by
reverse phase chromatography gave inhibitory activities as high as
86.3±2.0 for lentil, 94.8±1.8% for whey and 93.7±1.7% at 5th day of germination. Further purification by HPLC resulted in several
inhibitory peptides with IC50 values ranging from 0.064 to 0.164
mg/ml. These results demonstrate that lentil proteins are a good
source of peptides with ACE inhibitory activity that can be released by germination or gastrointestinal digestion. Despite the lower bioactivity in comparison with whey proteins, incorporation of lentil proteins in functional food formulations and natural drugs look promising.