• Journal of Integrative Natural Science
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• v.9 no.3
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• pp.190-198
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• 2016

Xanthine Oxidase is an enzyme, which oxidizes hypoxanthine to xanthine, and xanthine to uric acid. It is widely distributed throughout various organsincluding the liver, gut, lung, kidney, heart, brain and plasma. It is involved in gout pathogenesis. In this study, we have performed Comparative Molecular Field Analysis (CoMSIA) on a series of 2-(indol-5-yl) thiazole derivatives as xanthine oxidase (XO) inhibitors to identify the structural variations with their inhibitory activities. Ligand based CoMSIA models were generated based on atom-by-atom matching alignment. In atom-by-atom matching, the bioactive conformation of highly active molecule 11 was generated using systematic search. Compounds were aligned using the bioactive conformation and it is used for model generation. Different CoMSIA models were generated using different alignments and the best model yielded across-validated $q^2$ of 0.698 with five components and non-cross-validated correlation coefficient ($r^2$) of 0.992 with Fisher value as 236.431, and an estimated standard error of 0.068. The predictive ability of the best CoMSIA models was found to be $r{^2}_{pred}$ 0.653. The study revealed the important structural features required for the biological activity of the inhibitors and could provide useful for the designing of novel and potent drugs for the inhibition of Xanthine oxidase.

• Journal of Integrative Natural Science
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• v.15 no.4
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• pp.145-152
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• 2022

Colon rectal cancer is one of the frequently diagnosed cancers worldwide. In recent times the drug discovery for colon cancer is challenging because of their speedy metastasis and morality of these patients. C-jun N-terminal kinase signaling pathway controls the cell cycle survival and apoptosis. Evidence has shown that JNK1 promotes the tumor progression in various types of cancers like colon cancer, breast cancer and lung cancer. Recent study has shown that inhibiting, JNK1 pathway is identified as one of the important cascades in drug discovery. One of the recent approaches in the field of drug discovery is drug repurposing. In drug repurposing approach we have virtually screened ChEMBL dataset against JNK1 protein and their interactions have been studied through Molecular docking. Cross docking was performed with the top compounds to be more specific with JNK1 comparing the affinity with JNK2 and JNK3.The drugs which exhibited higher binding were subjected to Conceptual - Density functional theory. The results showed mainly Entrectinib and Exatecan showed better binding to the target.

• Analytical Science and Technology
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• v.21 no.6
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• pp.502-509
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• 2008

An ID LC/MS (isotope dilution liquid chromatography/mass spectrometry) was used as a primary method for the quantitative analysis of cholesterol in human serum. The separation of cholesterol was carried out by Thermo ODS hypersil $C^{18}$ column. The mobile phase was 100% methanol, and flow rate was $0.3m{\ell}/min$. Cholesterol and cholesterol-$3,4-13C_2$ were monitored at m/z 369.4 and 371.3, which correspond to $[M-H_2O+H]^+$ respectively. In order to verify the measurement method, NIST SRM 909b was analyzed. The results agreed well with certified values within uncertainty. The four kinds of serum certified reference material were prepared and certified. The repeatabilities of measurement were ranged from 0.1 to 0.8% (RSD), which were relatively good. The reproducibility between independent measurement run was below 0.24% (RSD). The expanded uncertainty was about 1.43% within the 95% confidence interval.

• Tunnel and Underground Space
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• v.29 no.5
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• pp.346-355
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• 2019

When evaluating pillar stability in very closely spaced tunnels, a local safety factor (strength/stress ratio) at the minimum width has been widely used. Tension bolts have been frequently applied as reinforcement for the cases where safety factors are less than 1.0 from FEM stress analysis. However, the local safety factor shows a constant value irrespective of the change in pillar width/tunnel diameter (PW/D) and the safety factor of the pillar is underestimated because the variation of deviation stress is relatively small even when the pre-stressing is applied to the tension bolt. In addition, the average safety factor proposed by Hoek and Brown(1980) was reviewed, but the pillar safety factor was relatively overestimated when the width of the pillar was increased. As an alternative, the SRM safety factor using shear strength reduction method shows the effect of changing the safety factor in the case of no reinforcement and tension bolt reinforcement as the pillar width/tunnel diameter(PW/D) changes. The failure shape is also similar to the previous limit theory result. In this study, the safety factor was evaluated without considering rock bolt and shotcrete to distinguish reinforcing effect of tension bolt.

• Analytical Science and Technology
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• v.20 no.1
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• pp.33-40
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• 2007

This study centered on the quantitative analysis of about 27 trace elements including toxic ones using instrumental neutron activation analysis of fine ambient particulate matter in the third and fourth industrial complex area of Daejeon city, Korea. For analytical quality control, the certified reference material (NIST, the National Institute of Standards and Technology, U.S.A., SRM 2783, air particulate on filter media) was used. The errors relative to SRM values of Sb, Mn, V, Mg, Na, K, Ti, Co, Zn, and Sm fell below 5%, while those of Cr, Fe, Ba, Th, Ce, Al, and Cu were less than 10%. From the results of the quantitative analysis, the concentration of toxic metals such as As, Mn, Se, V, and Zn were $3.26{\pm}2.72$, $9.86{\pm}4.71$, $2.18{\pm}1.25$, $4.91{\pm}2.41$, $158{\pm}78ng/m^3$, respectively. And the results of factor analysis indicated that there are no more than six factors of sources of fine ambient particulate with statistical significance in the study area.

• Journal of Integrative Natural Science
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• v.16 no.3
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• pp.81-95
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• 2023

Colorectal cancer is one of the most common types of cancer worldwide, ranking third after lung and breast cancer in terms of global prevalence. With an expected 1.93 million new cases and 935,000 deaths in 2020, it is more prevalent in males than in women. Evidence has shown that during the later stages of colon cancer, STAT1 promotes tumor progression by promoting cell survival and resistance to chemotherapy. Recent studies have shown that inhibiting STAT1 pathway leads to a reduction in tumor cell proliferation and growth, and can also promote apoptosis in colon cancer cells. One of the recent approaches in the field of drug discovery is drug repurposing. In drug repurposing approach we have virtually screened FDA database against STAT1 protein and their interactions have been studied through Molecular docking. Cross docking was performed with the top 10 compounds to be more specific with STAT1 comparing the affinity with STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6. The drugs that showed higher affinity were subjected to Conceptual - Density functional theory. Besides, the Molecular dynamic simulation was also carried out for the selected leads. We also validated in-vitro against colon cancer cell lines. The results showed mainly Acetyldigitoxin has shown better binding to the target. From this study, we can predict that the drug Acetyldigitoxin has shown noticeable inhibitory efficiency against STAT1, which in turn can also lead to the reduction of tumor cell growth in colon cancer.

• Journal of Integrative Natural Science
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• v.9 no.2
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• pp.121-127
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• 2016

CXC chemokine receptor 2 (CXCR2) is a prominent chemokine receptor on neutrophils. The neutrophilic inflammation in the lung diseases is found to be largely regulated through CXCR2 receptor. Antagonist of CXCR2 may reduce the neutrophil chemotaxis and alter the inflammatory response. Hence, in the present study, ligand based Comparative molecular field analysis (CoMFA) was performed on a series of CXCR2 antagonist named pyrimidine-5-carbonitrile-6-alkyl derivatives. The optimum CoMFA model was obtained with statistically significant cross-validated coefficients ($q^2$) of 0.568 and conventional coefficients ($r^2$) of 0.975. The contour maps suggest the important structural modifications and this study can be used to guide the development of potent CXCR2 antagonist.

• Journal of Integrative Natural Science
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• v.10 no.2
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• pp.105-109
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• 2017

Urotensin-2 receptor (UTS2R) is the most potent vasoconstrictor and plays a major role in the pathophysiology of various cardiovascular diseases and becomes a potential target for human pharmacotherapy. Hence, we have performed molecular docking of six antagonists with different inhibitory activity against UTS2R into its binding site. The binding mode of these antagonists was obtained using Surflex dock program interfaced in Sybyl-X2.0. The residues such as GLN278, THR304, TYR305, THR300, LEU299, CYS302, ASP47, TYR100 and THR304 are found in interaction between UTS2R and its antagonists. This study could be useful for identifying and analyzing the important residues involved in binding site of UTS2R receptor.

• Journal of Integrative Natural Science
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• v.10 no.4
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• pp.202-208
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• 2017

Xanthine Oxidase is an enzyme, which oxidizes hypoxanthine to xanthine, and xanthine to uric acid. It is widely distributed throughout various organs including the liver, gut, lungs, kidney, heart, brain and plasma. It is involved in gout pathogenesis. Hence, in the present study, Hologram based Quantitative Structure Activity Relationship Study was performed on a series of Xanthine Oxidase antagonist named 2-(indol-5-yl) thiazole derivatives. The best HQSAR model was obtained using Atoms, Bonds, Connection, Hydrogen, Chirality and Donor Acceptor as fragment distinction parameter using hologram length 71 and 4 components with fragment size of minimum 2 and maximum 5. Significant cross-validated correlation coefficient ($q^2$= 0.563) and non cross-validated correlation coefficients ($r^2$= 0.967) were obtained. The model was then used to evaluate the six external test compounds and its $r^2{_{pred}}$ was found to be 0.798. Contribution map show that presence of propyl ring in indole thiazole makes big contributions for improving the biological activities of the compounds. We hope that our HQSAR model and analysis will be helpful for future design of xanthine oxidase antagonists.

• Journal of Integrative Natural Science
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• v.10 no.4
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• pp.209-215
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• 2017

CXC chemokine receptor 2 (CXCR2) is a prominent chemokine receptor on neutrophils. CXCR2 antagonist may reduce the neutrophil chemotaxis and alter the inflammatory response because the neutrophilic inflammation in the lung diseases is found to be largely regulated through CXCR2 receptor. Hence, in the present study, Topomer based Comparative Molecular Field Analysis (Topomer CoMFA) was performed on a series of CXCR2 antagonist named pyrimidine-5-carbonitrile-6-alkyl derivatives. The best Topomer COMFA model was obtained with significant cross-validated correlation coefficient ($q^2$ = 0.487) and non cross-validated correlation coefficients ($r^2$ = 0.980). The model was evaluated with six external test compounds and its $r^2{_{pred}}$ was found to be 0.616. The steric and electrostatic contribution map show that presence of bulkier and electropositive group around cyclopropyl ring may contribute more for improving the biological activities of these compounds. The generated Topomer CoMFA model could be helpful for future design of novel and structurally related CXCR2 antagonists.