• Archives of Pharmacal Research
• /
• v.21 no.4
• /
• pp.445-451
• /
• 1998

A series of 5-hydroxy-4-quinolone (3) and 5-methoxy-4-quinolone (4) derivatives were synthesized as truncated acridone analogues and evaluated for antitumor, antiheroes and antituberculosis activities. Among them 5-hydroxy-8-methoxy-quinolone showed potent antitumor activity ($IC_{50}$=17.7 $\mu\textrm{M}$ for HL60) which was greater than that of acronycine. However, these compounds didn't show any significant antiheroes or antituberculosis activity.

• Archives of Pharmacal Research
• /
• v.27 no.5
• /
• pp.502-506
• /
• 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%).

• Journal of Microbiology and Biotechnology
• /
• v.25 no.6
• /
• pp.946-950
• /
• 2015

Recently, it has become a struggle to treat tuberculosis with the current commercial antituberculosis drugs because of the increasing emergence of multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis. We evaluated here the antimycobacterial activity of tamoxifen, known as a synthetic anti-estrogen, against eight drugsensitive or resistant strains of Mycobacterium tuberculosis (TB), and the active intracellular killing of tamoxifen on TB in macrophages. The results showed that tamoxifen had antituberculosis activity against drug-sensitive strains (MIC, 3.125-6.25 µg/ml) as well as drugresistant strains (MIC, 6.25 to 12.5 µg/ml). In addition, tamoxifen profoundly decreased the number of intracellular TB in macrophages in a dose-dependent manner.

• Tuberculosis and Respiratory Diseases
• /
• v.41 no.5
• /
• pp.489-493
• /
• 1994

Background: Nicotinamide adenine dinucleotide glycohydrolase(NADase) is located on the surface of the cells. It is bound by glycosylphosphatidylinositol(GPI)-linkage, which can be cleaved by bacterial PI-specific phospholipase C(PI-PLC). Recently, it was studied that NADase was increased in infected tuberculosis animal, but absolute NADase is uncertainly increased because of high NADase in Mycobacterium tuberculosis. Therefore, we studied pure NADase activity in red blood cells of normal person and patients of tuberculosis. Method: We evaluated the 19 healthy adults and 16 tuberculosis infected patients, and then, the latter cases were evaluated after 3 months antituberculosis therapy. NADase activity was calculated by scintillated counting of cleaved radioactive [carbonyl-$^3H$] nicotinamide Result: NADase activity was $2021.1{\pm}824.0\;pmol/min/10^6$ erythrocytes in healthy adults vs. $3339.0{\pm}1568.0$ in tuberculosis infected patients, and was $3339.0{\pm}1568.0$ in pretreated patients vs. $2238.6{\pm}1013.1$ in same 3 months treated patients. Conclusion: NADase activity of erythrocytes is elevated in tuberculosis infection, and normalized afer antituberculosis therapy. Therefore, we suggested NADase activity as the new diagnostic and therapeutic indicator.

• YAKHAK HOEJI
• /
• v.16 no.4
• /
• pp.162-175
• /
• 1972

Fifty six compounds of 4-methylthiosemicarbazone and thiorcarbohydrazone derivatives were prepared and subjected to biological tests. The following five compounds, 2-hydroxybenzaldehyde monothiocarbohydrazone (2),4-methylbenzaldehyde monothiocarbohydrazone (8), 1-(2-hydroxybenzaldehyde)-5(4-hydroxy-3-methoxybenzaldehyde) dithiocarbohydrazone (45), 1-(2-hydroxybenzaldehyde)-5-furfural dithiocarbohydrazone (46) and 1-benzaldehyde-5-cinnamaldehyde dithiocarbohydrazone (49) exhibited marked antimicrobial activity against E. coli, St. aureus and P. chrysogenum. In addition to these compounds, 3-methoxybenzaldehyde monothiocarbohydrazone (12) and 4-methylbenzaldehyde dithiocarbohydrazone (29) showed marked inhibition of HeLa cell growth at the concentration of 10 ${\nu}$g/ml. It was generally observed that most compounds demonstrated significant antifungal activity against P. chrysongenum but only one compound, 3-hydroxy-4-methoxybenzaldehyde dithiocarbohydrazone (39), exerted antituberculosis activity against M. tuberculosis H$_{37}$ RV at the concentration of 10 ${\nu}$g/ml.

• Journal of Preventive Medicine and Public Health
• /
• v.26 no.1 s.41
• /
• pp.49-64
• /
• 1993

To provide the basic data for assessment of renal dysfunction related to silicosis, urinary N-acetyl-$\beta$-D-giucobarninidase(NAG) activity known as a sensitive markers for early renal damage were measured in 58 silicosis patients, and control subjects of 40 pulmonary tuberculosis Patients and 51 official workers. The results were summarized as fellows. 1. The values of blood urea nitrogen and serum creatinine in all subjects were within reference limits. But the mean value of urinary NAG activity($7.25{\pm}7.31U/g\;creatinine$) was beyond reference value and more sensitive test than others. 2. The mean value of urinary NAG activity in silicosis group was $11.98{\pm}9.05U/g\;creatinine$ and significantly higher than in tuberculosis and healthy group(p<0.01), but the mean values of NAG activity in tuberculosis and healthy group were not different(p>0.05). 3. The value of NAG activity in tuberculosis had a tendency to be increased according to severity of disease, but that was not significant(p>0.05). The value of NAG activity was increased significantly by use of nephrotoxic antituberculosis drugs(p<0.05). 4. The value of NAG activity in silicosis had a tendecy to be increased according to the size of nodule, use of nephrotoxic antituberculosis drugs and shortness of onset duration, but the increase was not significant(p>0.05). 5. After excluding the users of nephrotoxic antituberculosis drugs, the mean values of NAG activity in healthy control and in tuberculosis control were same as 3.63 U/g creatinine and 3.60 U/g creatinine, respectively. But the mean value of NAG activity in silicosis group was remarkably increased as 10.90 U/g creatinine(p<0.01). As above results, even though there are no abnormal finding in screening renal function test, silicosis can be related with renal dysfunction. And it will be very useful to apply urinary NAG activity in health management of workers exposed to dust.

• Journal of Chest Surgery
• /
• v.11 no.1
• /
• pp.12-17
• /
• 1978

Rifampicin has been widely hailed as the most effective antituberculosis antibiotics since the clinical use of streptomycin, but its immunosuppressive side effect was still annoying problem to be excluded. These studies were carried out to determine the effect of Tuberein-3, tuberculous bacilli extraction with water, on Rifampicin induced T-lymphocytopenia in 5 cases of pulmonary tuberculosis who have never exposed to antimetabolites or steroid compounds. After 2 weeks treatment of Rifampicin, all cases showed T-lymphocytopenia, active $13.0{\pm}2.3$ % and total $43.1{\pm}4.4$%. Followed by another 2 weeks treatment with Rifampicin combined with Tuberein-3, T-lymphocytes in peripheral blood returned to the normal limit, active $21.6{\pm}3.3$% and total $56.3{\pm}1.7$%. Tubercin-3 revealed the restoring activity of suppression of T-lymphocyte rosettes by Rifampicin.

• Tuberculosis and Respiratory Diseases
• /
• v.65 no.6
• /
• pp.522-526
• /
• 2008

A 63-year old woman was admitted to our hospital for an evaluation of thrombocytopenia. She had been diagnosed with tuberculous pericarditis three months earlier in a local clinic and treated with anti-tuberculosis medication. Two months later, thrombocytopenia developed. The medication was subsequently stopped because it was suspected that the anti-tuberculosis medication, particularly rifampin, might have caused the severe platelet reduction. However, the thrombocytopenia was more aggravated. A bone marrow biopsy was performed, which showed moderate amounts of histiocytes with active hemophagocytosis. This finding strongly suggested that the critical thrombocytopenia had been caused by hemophagocytic syndrome, not by the side effects of the anti-tuberculosis medication. Furthermore, the development of hemophagocytosis might have been due to an uncontrolled tuberculosis infection and its associated aberrant immunity. Therefore, she was started with both standard anti-tuberculosis medication and chemotherapy using etoposide plus steroid. One month after the initiation of treatment, the thrombocytopenia had gradually improved and she was discharged in a tolerable condition. At the third month of the follow-up, her platelet level and ferritin, the activity marker of hemophagocytic syndrome, was within the normal range.

• Bulletin of the Korean Chemical Society
• /
• v.28 no.6
• /
• pp.947-952
• /
• 2007

Mycobacterium tuberculosis is a pathogen responsible for 2-3 million deaths every year worldwide. The emergence of drug-resistant and multidrug-resistant tuberculosis has increased the need to identify new antituberculosis targets. Acetohydroxy acid synthase, (AHAS, EC 2.2.1.6), an enzyme involved in branched-chain amino acid synthesis, has recently been identified as a potential anti-tuberculosis target. To assist in the search for new inhibitors and “receptor-based” design of effective inhibitors of tubercular AHAS (TbAHAS), we constructed four different structural models of TbAHAS and used one of the models as a target for virtual screening of potential inhibitors. The quality of each model was assessed stereochemically by PROCHECK and found to be reliable. Up to 89% of the amino acid residues in the structural models were located in the most favored regions of the Ramachandran plot, which indicates that the conformation of each residue in the models is good. In the models, residues at the herbicide-binding site were highly conserved across 39 AHAS sequences. The binding mode of TbAHAS with a sulfonylurea herbicide was characterized by 32 hydrophobic interactions, the majority of which were contributed by residue Trp516. The model based on the highest resolution X-ray structure of yeast AHAS was used as the target for virtual screening of a chemical database containing 8300 molecules with a heterocyclic ring. We developed a short list of molecules that were predicted to bind with high scores to TbAHAS in a conformation similar to that of sulfonylurea derivatives. Five sulfonylurea herbicides that were calculated to efficiently bind TbAHAS were experimentally verified and found to inhibit enzyme activity at micromolar concentrations. The data suggest that this time-saving and costeffective computational approach can be used to discover new TbAHAS inhibitors. The list of chemicals studied in this work is supplied to facilitate independent experimental verification of the computational approach.

• Tuberculosis and Respiratory Diseases
• /
• v.40 no.5
• /
• pp.509-518
• /
• 1993

Background: By amplifying small amount of DNA, polymerase chain reaction (PCR) can be used for the detection of very small amount of microbial agent, and may be especially useful in certain cases which are difficult to be diagnosed microbiologically or serologically. Tuberculous pleurisy is a disease that can be diagnosed in only 70% of cases by conventional diagnostic tools, and PCR would be a very rapid, easy, and sensitive diagnostic method. Method: The specificity and sensitivity of PCR to detect Mycobacterium tuberculosis DNA were evaluated using various strains of Mycobacteria. To evaluate the diagnostic usefulness of PCR in tuberculous pleurisy, we used PCR to detect Mycobacterium tuberculosis DNA in pleural fluid. The amplification target was 123 base pair DNA, a part of IS6110 fragment, 10~16 copies of which are known to exist per genome. The diagnostic yield of PCR was compared with conventional methods, including pleural fluid adenosine deaminase (ADA) activity. Also, the significance of PCR in undiagnosed pleural effusion was evaluated prospectively with antituberculosis treatment. Results: 1) Using cultured Mycobacterium tuberculosis and other strains, PCR could detect upto 1 fg DNA and specific for only Mycobacterium tuberculosis and Mycobacterium bovis. 2) Using pleural effusions of proven tuberculosis cases, the sensitivity of PCR was 80.0% (16/20), and the specificity 95.0% (19/20). 3) Among 13 undiagnosed, but suspected tuberculous effusion, the positive rate was 60% in 10 improved cases after antituberculosis medications, and 0% in 3 cases of proven malignancy later. 4) Adenosine deaminase level of proven and clinically diagnosed tuberculous pleurisy patients was significantly higher than that of excluded patients, and correlated well with PCR results. Conclusion: We can conclude that PCR detection of Mycobacterium tuberculosis in pleural effusion has acceptable sensitivity and specificity, and could be an additional diagnostic tool for the diagnosis of tuberculous pleurisy.