• Bulletin of the Korean Chemical Society
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• v.27 no.2
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• pp.273-276
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• 2006

Three dimensional quantitative structure-activity relationship studies for a series of isatin derivatives as a nonpeptidyl caspase-3 enzyme inhibitor were investigated using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The first approach of non-peptidyl small molecules by 3D QSAR may be useful in guiding further development of potent caspase-3 inhibitors.

• The Korean Journal of Pesticide Science
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• v.6 no.3
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• pp.209-217
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• 2002

Two different QSAR methods, the comparative molecular similarity indices analyses (CoMSIA) and hologram quantitative structure activity relationship (HQSAR) are studied for the fungicidal activities ($pI_{50}$) of 2-N-benzyl-5-phenoxy-3-isothiazolone derivatives against sensitive (SPC: 95CC7105) and resisitive (RPC: 95CC7303) phytophthora blight fungus (Phytaphthora capsici). According to the findings from these QSAR investigation, the cross-validation value, $q^2$ and Pearson correlation coefficient, $r^2$ in the two methods were CoMSIA: RPC; $q^2=0.675,\;r^2=0.942$, SPC; $q^2=0.350,\;r^2=0.876$ and HQSAR: RPC; $q^2=0.519,\;r^2=0.869$, SPC; $q^2=0.483,\;r^2=0.990$, respectively. Therefore, the two models of comparative statistical significance were obtained. From the CoMSIA contour maps, the important factors for selective fungicidal activity against RPC are to be expected that the lower hydrophobic and not bulkiness substituent as hydrogen bonding acceptor have to introduce to meta and para-position (C1-C6) on the phenoxy moiety. And the results of prediction suggest that HQSAR method showed higher fungicidal activity than CoMSIA method.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.1
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• pp.55-59
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• 2009

Three dimensional quantitative structure activity relationship between diazabicyclo[4.2.0]octanes and nicotinic acetylcholine receptor($h{\alpha}4{\beta}2$ and $h{\alpha}3{\beta}4$) agonists was studied using comparative molecular field analysis(CoMFA) and comparative molecular similarity indices analysis(CoMSIA). From 11 CoMFA and CoMSIA models, CoMSIA with steric and electrostatic fields gave the best predictive models($q^2=0.926$ and 0.945, ${r^2}_{ncv}=0.983$ and 0.988). This study can be used to develop potent $h{\alpha}4{\beta}2$ receptor agonists with low activity on $h{\alpha}3{\beta}4$ subtype.

• Journal of Integrative Natural Science
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• v.9 no.3
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• pp.177-184
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• 2016

CXC chemokine receptor 2 (CXCR2) is a prominent chemokine receptor on neutrophils and it regulates the neutrophilic inflammation in the lung diseases. CXCR2 antagonist may reduce the neutrophil chemotaxis and alter the inflammatory response. Hence, in the present study, ligand based Comparative Molecular Similar Indices Analysis (CoMSIA) was performed on a series of CXCR2 antagonist named pyrimidine-5-carbonitrile-6-alkyl derivatives. The optimum CoMSIA model was obtained with statistically significant cross-validated coefficients ($q^2$) of 0.582 and conventional coefficients ($r^2$) of 0.987 with steric, electrostatic, hydrophobic, donor and acceptor fields. The contour maps suggest the important structural modifications and this study can be used to guide the development of potent CXCR2 antagonist.

• Molecular & Cellular Toxicology
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• v.2 no.3
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• pp.216-221
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• 2006

The cholinesterase-inhibiting organophosphorous (OP) compounds known as nerve agents are highly toxic. The principal toxic mechanism of OP compounds is the inhibition of acethylcholine esterase (AChE) by phosphorylation of its catalytic site. The reversible competitive inhibition of AChE may prevent the subsequent OP intoxication. In this study, three-dimensional quantitative structure-activity relationship (3D-QSAR) was performed to investigate the relationship between the 29 compounds with structural diversity and their bioactivities against AChE. In particular, predictive models were constructed using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The results indicate reasonable model for CoMFA ($q^{2}=0.453,\;r^{2}=0.697$) and CoMSIA ($q^{2}=0.518,\;r^{2}=0.696$). The presence of steric and hydophobic group at naphtyl moiety of the model may lead to the design of improved competitive inhibitors for organophosphorous intoxication.

• Bulletin of the Korean Chemical Society
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• v.34 no.4
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• pp.1212-1220
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• 2013

The human coagulation factor XI (FXI) is a serine protease that plays a significant role in blocking of the blood coagulation cascade as an attractive antithrombotic target. Selective inhibition of FXIa (an activated form of factor XI) disrupts the intrinsic coagulation pathway without affecting the extrinsic pathway or other coagulation factors such as FXa, FIIa, FVIIa. Furthermore, targeting the FXIa might significantly reduce the bleeding side effects and improve the safety index. This paper reports on a docking-based three dimensional quantitative structure activity relationship (3D-QSAR) study of the potent FXIa inhibitors, the chloro-phenyl tetrazole scaffold series, using comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) methods. Due to the characterization of FXIa binding site, we classified the alignment of the known FXIa inhibitors into two groups according to the docked pose: S1-S2-S4 and S1-S1'-S2'. Consequently, highly predictive 3D-QSAR models of our result will provide insight for designing new potent FXIa inhibitors.

• Bulletin of the Korean Chemical Society
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• v.25 no.12
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• pp.1801-1806
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• 2004

Ligand-based quantitative structure-activity relationship (QSAR) studies were performed on indolinones derivatives as a potential inhibitor of the protein tyrosine kinase of fibroblast growth factor receptor (FGFR) by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) implemented in the SYBYL packages. The initial X-ray structure of docked ligand (Su5402) to FGFR was used to minimize the 27 training set molecules using TRIPOS force field. Seven models were generated using CoMFA and CoMSIA with grid spacing 2 ${\AA}$. After the PLS analysis the best predicted CoMSIA model with hydrophobicity, hydrogen bond donor and acceptor property showed that a leave-one out(LOO) cross validated value $({r^2}_{cv})^$ and non-cross validated conventional value $({r^2}_{ncv})^$ are 0.543 and 0.938, respectively.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.65.2-65.2
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• 2003

88 selective COX-2 inhibitors belonging to three chemical classes (triaryl rings, diaryl cycloalkanopyrazoles, and diphenyl hydrazides) were studied using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Partial least squares analysis produced statistically significant models with q values of 0.84 and 0.79 for CoMFA and CoMSIA, respectively. The key spatial properties were detected by careful analysis of the isocontour maps. The binding energies calculated from flexible docking correlated with inhibitory activities by the least-squares fit method. (omitted)

• Bulletin of the Korean Chemical Society
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• v.32 no.2
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• pp.645-650
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• 2011

The 3D-QSAR study of 2-arylbenzoxazoles as novel cholesteryl ester transfer protein inhibitors was performed by comparative molecular field analysis (CoMFA), CoMFA region focusing (CoMFA-RF) for optimizing the region for the final PLS analysis, and comparative molecular similarity indices analysis (CoMSIA) methods to determine the factors required for the activity of these compounds. The best orientation was searched by all-orientation search strategy using AOS, to minimize the effect of the initial orientation of the structures. The predictive ability of CoMFARF and CoMSIA were determined using a test set of twelve compounds giving predictive correlation coefficients of 0.886, and 0.754 respectively indicating good predictive power. Further, the robustness and sensitivity to chance correlation of the models were verified by bootstrapping and progressive scrambling analyses respectively. Based upon the information derived from CoMFA(RF) and CoMSIA, identified some key features that may be used to design new inhibitors for cholesteryl ester transfer protein.

• Bulletin of the Korean Chemical Society
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• v.30 no.11
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• pp.2739-2748
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• 2009

Hologram and three dimensional quantitative structure activity relationship (3D QSAR) studies for a series of anilinobipyridine JNK3 inhibitors were performed using various alignment-based comparative molecular field analysis (COMFA) and comparative molecular similarity indices analysis (CoMSIA). The in vitro JNK3 inhibitory activity exhibited a strong correlation with steric and electrostatic factors of the molecules. Using four different types of alignments, the best model was selected based on the statistical significance of CoMFA ($q_2\;=\;0.728,\;r_2\;=\;0.865$), CoMSIA ($q_2\;=\;0.706,\;r_2\;=\;0.960$) and Hologram QSAR (HQSAR: $q_2\;=\;0.838,\;r_2\;=\;0.935$). The graphical analysis of produced CoMFA and CoMSIA contour maps in the active site indicated that steric and electrostatic interactions with key residues are crucial for potency and selectivity of JNK3 inhibitors. The HQSAR analysis showed a similar qualitative conclusion. We believe these findings could be utilized for further development of more potent and selective JNK3 inhibitors.