• Journal of the Korean Chemical Society
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• v.66 no.3
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• pp.194-201
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• 2022

A simple, efficient, and cost-effective method has been employed for the synthesis of 2,4,5-trisubstituted imidazole derivatives (3a-j) containing quinoline substituent at 2^nd position. Title compounds were obtained by multicomponent reaction (MCR), involving aryl substituted 1,2-diketone, quinoline carbaldehyde and ammonium acetate in the presence of acetic acid solvent under mild reaction conditions. The newly synthesized quinoline containing imidazole derivatives were confirmed through FT-IR, ¹H-NMR, ¹³C-NMR and mass spectral analysis. In-vitro microplate alamar blue assay (MABA) to determine the MIC (minimum inhibitory concentration) values against Mycobacterium tuberculosis H37Rv was performed for the synthesized compounds. The synthesized compounds exhibited activity against Mycobacterium tuberculosis and among which compounds, 3d, 3f and 3i showed good activity. The highest activity was showed with compound 3i. The anti-mycobacterial activity results are well correlated with the computational molecular docking analysis, which was performed for the synthesized compounds prior to the evaluation of the activity.

• Archives of Pharmacal Research
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• v.27 no.5
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• pp.502-506
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• 2004

Two series of 2-(5-nitro-2-furyl)- and 2-(1-methyl-5-nitro-1H-imidazol-2-yl)-5-propyl, allyl and propargyl)thio-1,3,4-thiadiazoles (6a-f) and 2-(5-nitro-2-furyl)- and 2-(1-methyl-5-nitro-1 H-imidazol-2-yl)-5-(nitrobenzyl)thio-1,3,4-thiadiazole derivatives (8a-f) have been synthesized and evaluated against Mycobacterium tuberculosis, as part of the TAACF TB screening program under direction of the US National Institute of Health, the NIAID division. Primary screening was conducted at a single concentration, 6.25 $\mu\textrm{g}$mL$^{-1}$ , against M. tuberculosis H$_{37}$ Rv in BACTEC 12B medium, using the Microplate Alamar Blue Assay (MABA). The minimum inhibitory concentration (MIC) was determined for the compounds that demonstrated $\geq$90% growth inhibition in the primary screening. A varying degree of antituberculosis activity (from 0-97% of growth inhibition) was observed with the alkylthio series (6a-f), and the nitroimidazole derivative with a propylthio group (6b) and the nitrofuran derivative with a propargylthio group (6e), were the most active compounds (MIC=3.13 and 1.56 /$\mu\textrm{g}$mL$^{-1}$ , respectively). Among the nitrobenzylthio derivatives (8a-f), all the ortho, meta and para nitrobenzyl isomers in the nitrofuran series exhibited good antituberculosis activity (MIC=3.13 $\mu\textrm{g}$mL$^{-1}$ ), while the corresponding nitroimidazole analogues were completely inactive (Inhibition=0%).

• The Journal of the Korean Society for Microbiology
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• v.34 no.6
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• pp.561-571
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• 1999

Diagnosis of mycobacterial infection is dependent upon the isolation and identification of causative agents. The procedures involved are time consuming and technically demanding. To improve the laborious identification process mycobacterial systematics supported by gene analysis is feasible, being particularly useful for slowly growing or uncultivable mycobacteria. To complement genetic analysis for the differentiation and identification of mycobacterial species, an alternative marker gene, rpoB encoding the ${\beta}$ subunit of RNA polymerase, was investigated. rpoB DNAs (342 bp) were amplified from 52 reference strains of mycobacteria including Mycobacterium tuberculosis H37Rv (ATCC 27294) and clinical isolates by the PCR. The nucleotide sequences were directly determined (306 bp) and aligned using the multiple alignment algorithm in the MegAlign package (DNASTAR) and MEGA program. A phylogenetic tree was constructed with a neighborhood joining method. Comparative sequence analysis of rpoB DNA provided the basis for species differentiation. By being grouped into species-specific clusters with low sequence divergence among strains belonging to same species, all the clinical isolates could be easily identified. Furthermore RFLP analysis enabled rapid identification of clinical isolates.

• Biomedical Science Letters
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• v.15 no.4
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• pp.295-300
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• 2009

Tuberculosis caused by Mycobacterium tuberculosis (MTB) still remains to be the most dreadful infectious disease affecting almost every country. In the present study, we developed a simple and rapid but accurate and sensitive assay method for detecting MTB using microplate hybridization assay. For this, a selective region of the rpoB gene was used to design PCR primers, and MTB and Mycobacterium genus-specific probe molecules. The specificity of the assay was confirmed using fifteen different mycobacterial reference strains and twelve different non-mycobacterial reference strains, and the sensitivity was determined to be 100 fg using genomic DNA of MTB reference strain, H37Rv. Subsequently, a total of 62 sputum samples with diverse smear scores and culture positive results were used to evaluate the kit performance. In brief, the specificity and the sensitivity of the assay were 100% and 98.4%, respectively.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.8
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• pp.1097-1102
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• 2008

Paraoxonase-1 (PON1), like lipoprotein lipase (LPL), plays a key role in the metabolism and physiology of mammalian growth. The objectives of this study were to estimate the allele and genotype frequencies at the PON1/EcoRV and PON1/AluI loci in three genetic groups of beef cattle and to determine associations between these polymorphisms and growth and carcass traits. Genotyping was performed on 30 Angus, 32 Hereford and 26 Simmental. The association analysis was carried out using the GLM procedure of SAS 9.1 and the least squares means of the genotypes were compared by the Tukey's test. Animals with AG genotype at the PON1/EcoRV locus had higher weight at the time of entry into the fattening corrals ($329.97{\pm}6.08kg$) and close to the time of slaughter ($577.56{\pm}8.32kg$) and net meat weight ($275.89{\pm}4.05kg$) and fitted tenderness ($3.10{\pm}0.19kg$) (p<0.05). Animals with AA genotype at the PON1/AluI locus had higher weight at the time of entry ($333.37{\pm}8.93kg$) and slaughter ($576.82{\pm}13.18kg$) and net meat weight ($275.49{\pm}6.43kg$) and average daily gain ($0.68{\pm}0.02kg/d$) (p<0.05). The meat color score was also significantly higher (p<0.05). Between genotypes and breeds, there were significant differences observed except for TBW, REMG, MBS, REA and MCS. As a metabolism gene, genotypes of the SNPs of PON1 gene might be reflecting BFT directly, such as $A_eA_eG_aG_a$ genotype in this experiment.

• Pediatric Infection and Vaccine
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• v.17 no.2
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• pp.130-136
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• 2010

Purpose : The purpose of this study is to identify the viral etiology of acute respiratory illnesses and to determine epidemiology in outpatients in Busan, Korea. Methods : We collected nasal wash samples from 990 patients who visited the hospital for acute respiratory illnesses between January 2007 and December 2008. Extracted DNA or RNA from specimens was used for viral detection by an RT-PCR method. Results : Of a total of 990 samples, viruses were detected in 351 cases (35.5%). The ratio of male to female was 1.6:1 and 93.7% were less than 5 years old. Rhinovirus was detected year-round in 202 cases (57.5%), respiratory syncytial virus from October to March in 57 cases (16.2%), adenovirus year-round in 37 cases (10.5%), influenza virus from December to April in 21 cases (6%), bocavirus from January to August in 15 cases (4.3%), parainfluenza virus from April to July in 9 cases (2.6%), coronavirus from January to July in 7 cases (2%), and enterovirus from June to September in 3 cases (0.9%). Conclusion : We identified the etiology and epidemiology of viruses that caused the acute respiratory diseases that were prevalent in Busan, 2007-2008. Further surveillance will be necessary.

• IMMUNE NETWORK
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• v.5 no.4
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• pp.237-246
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• 2005

Background: Little information is available on the identification and characterization of the upstream regulators of the signal transduction cascades for Mycobacterium tuberculosis (M. tbc)-induced ERK 1/2 activation and chemokine expression. We investigated the signaling mechanisms involved in expression of CCL3 /MIP-1 and CCL4/MIP-1 in human primary monocytes infected with M. tbc. Methods: MAP kinase phosphorylation was determined using western blot analysis with specific primary antibodies (ERK 1/2, and phospho-ERK1/2), and the upstream signaling pathways were further investigated using specific inhibitors. Results: An avirulent strain, M. tbc H37Ra, induced greater and more sustained ERK 1/2 phosphorylation, and higher CCL3 and CCL4 production, than did M. tbc H37Rv. Specific inhibitors for mitogen-activated protein kinase (MAPK) kinase (MEK; U0126 and PD98059) significantly inhibited the expression of CCL3 and CCL4 in human monocytes. Mycobactetia-mediated expression of CCL3 and CCL4 was not inhibited by the Ras inhibitor manumycin A or the Raf-1 inhibitor GW 5074. On the other hand, phospholipase C (PLC) inhibitor (U73122) and protein kinase C (PKC)specific inhibitors ($G\ddot{o}6976$ and Ro31-8220) significantly reduced M. tbc-induced activation of ERK 1/2 and chemokine synthesis. Conclusion: These results are the first to demonstrate that the PLC-PKC-MEK-ERK, not the Ras-Raf-MEK-ERK, pathway is the major signaling pathway inducing M. tbc-mediated CCL3 and CCL4 expression in human primary monocytes.

• Journal of Life Science
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• v.15 no.4 s.71
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• pp.652-656
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• 2005

Tuberculosis is the leading infectious disease in the world. It is urgent to develop new vaccine and treating drugs. Besides vaccines, we want to know the effects of regular swim training on TB infection in the mouse model. This study was designed to examine the effects of regular swim training on lung and spleen TB counts and $INF-\gamma$ activity in the trained mice at different temperature. The trained mice underwent a 10-wk endurance swim training (5 times/wk) in water at $29\~33^{\circ}C$ (WWG) and $21\~23^{\circ}C$(CWG) for 60 min. And they were divided into 3 groups according to the regular swim training (CG; control, WWG; warm water group, and CWG; cold water group). Mice were challenged by aerosol infection with M. tuberculosis H37Rv using an inhalation device (Glas-Col, Terre Haute, Ind.) calibrated to deliver bacteria into lungs. Three weeks after immunization, the mice were challenged. Four weeks after challenge, the mice were sacrificed and the numbers of viable bacteria in lung and spleen were determined by plating serial dilution of whole organ homogenates on nutrient Middlebrook 7H11 agar (Difco, Detroit, MI). Colonies were counted after four weeks incubation at $37^{\circ}C$. All data were expressed as mean, standard deviation by using SPSS package program (win 10.0). The result through the statistical analysis of this data were summarized as follows; In the weight changes, there were significant differences among CG, WWG, and CWG following the swim training at different temperature, and CWG was the lowest. In the change of $INF-\gamma$ following the swim training, there were significant differences (p<.05) among CG, WWG, and CWG after stimulated with media and CFP. In MTB counts, there were significant differences (p<.05) between CG and WWG in the lung. And also there were significant differences (p<.05) among CG, WWG, and CWG. These results suggest that regular swim training suppress Th1 immune response caused by decreased $INF-\gamma$ level in the WWG, Also For the WWG, highly increased level of TB counts appear in the lung and spleen compare to CG.

• The Journal of the Korean Society for Microbiology
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• v.20 no.1
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• pp.65-72
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• 1985

Vitamin C is known as an integral element for the formation and maintenance of intercellular supporting structures. Ascorbic acid has been used for the treatment of certain poisonings and hypovitaminosis(scurvy) but also known as a powerful reducing agent, and can kill a variety of bacteria and detoxify bacterial exotoxins including various clostridial exotoxins in vitro. For viruses, vitamin C inactivates herpes virus, vaccinia virus and influenza virus and has been used for the prevention and treatment of the common cold. Thus ascorbic acid plays an important role in antimicrobial action. Scurvy also promotes the development of tubercles in experimentally infected guinea pig and the tuberculosis patients require more vitamin C than normal persons. However there is no reports that ascorbic acid could inhibit the growh of M. tuberculosis. In this paper, antibacterial effects of ascorbic acid against M. tuberculosis were studied. The results are as follows: 1. The single use of the ascorbic acid exhibited antibacterial effect in vitro against $5{\times}10^3/ml$ of M. tuberculosis $H_{37}$ Rv at the concentration of ascorbic acid 0.625mg/ml over 3 hours exposure and 0.05mg/ml over 9 hours exposure. 2. In vivo mice administered with ascorbic acid 50mg/day for 5, 10 and 15 days respectively were protected from M. tuberculosis $2LD_{50}$, $3LD_{50}$, $4LD_{50}$ and $5LD_{50}$ given intravenously.

• Journal of the Korean Chemical Society
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• v.56 no.2
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• pp.236-245
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• 2012

The main mycobacterial infection in human is tuberculosis caused by Mycobacterium tuberculosis. Tuberculosis is the leading infectious cause of death in the world. Therefore there is continuing and compelling need for new and improved treatment for tuberculosis. The entire logic towards design of new compounds containing 4-hydroxy-N'-(1,3-thiazoldin- 2-yldene)benzohydrazide moiety is basically for superior antimycobacterial activity. The recent advances in QSAR and computer science have provided a systematic approach to design a structure of any compound and further, the biological activity of the compound can be predicted before synthesis. The 3D-QSAR studies for the set of 4-hydroxy-N'-(1,3-thiazoldin- 2-yldene)benzohydrazide and their derivatives were carried out by using V-life MDS (3.50). The various statistical methods such as Multiple Linear Regression (MLR), Partial Least Square Regression (PLSR), Principle Component Regression(PCR) and K nearest neighbour (kNN) were used. The kNN showed good results having cross validated $r^2$ 0.9319, $r^2$ for external test set 0.8561 and standard error of estimate 0.2195. The docking studies were carried out by using Schrodinger GLIDE module which resulted in good docking score in comparison with the standard isoniazid. The designed compounds were further subjected for synthesis and biological evaluation. Antitubercular evaluation of these compounds showed that (4.a), (4.d) and (4.g) found as potent inhibitor of H37RV.