• 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.

• Journal of Integrative Natural Science
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• v.4 no.2
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• pp.91-98
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• 2011

Quantitative structure-activity relationships (QSAR) have been applied for two decades in the development of relationships between physicochemical properties of chemical substances and their biological activities to obtain a reliable statistical model for prediction of the activities of new chemical entities. The fundamental principle underlying the QSAR is that the structural difference is responsible for the variations in biological activities of the compounds. In this work, we developed 3D-QSAR model for a series of 5-Lipoxygenase inhibitors, utilizing comparative molecular field analysis (CoMFA) and Topomer CoMFA methodologies. Our developed models addressed superiority of Topomer CoMFA over CoMFA. The CoMFA model was obtained with $q^2$=0.593, $r^2$=0.939, $Q^2$=0.334 with 6 optimum number of components (ONC). Higher statistical results were obtained with the Topomer CoMFA model ($q^2$=0.819, $r^2$=0.947, ONC=5). Further robustness of developed models was checked with the ANOVA test and it shows F=113 for CoMFA and F=162.4 for Topomer CoMFA model. Contour map analysis indicated that the more requirement of electrostatic parameter for improved potency.

• 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.

• Bulletin of the Korean Chemical Society
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• v.33 no.2
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• pp.613-619
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• 2012

We applied several machine learning methods for developing QSAR models for prediction of acute toxicity to fathead minnow. The multiple linear regression (MLR) and artificial neural network (ANN) method were applied to predict 96 h $LC_{50}$ (median lethal concentration) of 555 chemical compounds. Molecular descriptors based on 2D chemical structure were calculated by PreADMET program. The recursive partitioning (RP) model was used for grouping of mode of actions as reactive or narcosis, followed by MLR method of chemicals within the same mode of action. The MLR, ANN, and two RP-MLR models possessed correlation coefficients ($R^2$) as 0.553, 0.618, 0.632, and 0.605 on test set, respectively. The consensus model of ANN and two RP-MLR models was used as the best model on training set and showed good predictivity ($R^2$=0.663) on the test set.

• Bulletin of the Korean Chemical Society
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• v.27 no.2
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• pp.266-272
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• 2006

Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were developed for 67 molecules of 2-amino-benzothiazole-6-anilide derivatives against lymphocyte-specific protein tyrosine kinase (P56 LCK). The molecular field analysis (MFA) and receptor surface analysis (RSA) were employed for QSAR studies and the predictive ability of the model was validated by 15 test set molecules. Structure-based investigations using molecular docking simulation were performed with the crystal structure of P56 LCK. Good correlation between predicted fitness scores versus observed activities was demonstrated. The results suggested that the nature of substitutions at the 2-amino and 6-anilide positions were crucial in enhancing the activity, thereby providing new guidelines for the design of novel P56 LCK inhibitors.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.250.1-250.1
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• 2003

In this work, we have conducted 3D-QSAR studies on a series of acanthonic acid derivatives that act as COX-2 inhibitors, using two different methods: comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). CoMFA and CoMSIA analysis of twenty five pimarane analogues produced good models with high predictive abilities. (omitted)

• Bulletin of the Korean Chemical Society
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• v.32 no.5
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• pp.1604-1612
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• 2011

We developed three-dimensional quantitative structure activity relationship (3D-QASR) models for 17 adamantyl derivatives as P-glycoprotein (P-gp) inhibitors. Eighteen different partial charge calculation methods were tested to check the feasibility of the 3D-QSAR models. Best predictive comparative molecular field analysis (CoMFA) model was obtained with the Austin Model 1-Bond Charge Correction (AM1-BCC) atomic charge. The 3D-QSAR models were derived with CoMFA and comparative molecular similarity indices analysis (CoMSIA). The final CoMFA model ($q^2$ = 0.764, $r^2$ = 0.988) was calculated with an AM1-BCC charge and electrostatic parameter, whereas the CoMSIA model ($q^2$ = 0.655, $r^2$ = 0.964) was derived with an AM1-BCC charge and combined steric, electrostatic, hydrophobic and HB-acceptor parameters. Leave-five-out (LFO) cross-validation was also performed, which yielded good correlation coefficient for both CoMFA (0.801) and CoMSIA (0.656) models. Robustness of the developed models was checked further with 1000 run bootstrapping analyses, which gave an acceptable correlation coefficient for CoMFA (BS-$r^2$ = 0.997, BS-SD = 0.003) and CoMSIA (BS-$r^2$ = 0.996, BS-SD = 0.018).

• Journal of the Korean Chemical Society
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• v.54 no.1
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• pp.77-87
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• 2010

Hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) has been an increasing problem worldwide since the initial reports over 40 years ago. To examine new drug leads with potential antibacterial activities, Various N'-[(-3-substituted-4-oxo-1,3-thiazolidin-2-ylidene]-4-hydroxy benzohydrazide (4a-4.i) and N'-[-(3,4-disubstituted)-1,3-thiazolidin-2ylidene)]-4-hydroxybenzohydrazide from (5.a-5.i) to (10.a-10.i) were synthesized using appropriate synthetic route. The entire test compounds (4.a-4.i) and from (5.a-5.i) to (10.a-10.i) were assayed in vitro against s. aureus strain. The minimum inhibitory concentration (MIC) was determined for test compounds and for reference standards. The test compounds showed significant antibacterial activity against the strains used, when tested in vitro. In general, p-hydroxybenzohydrazide ring and substituted thiazoline ring are essential for antimicrobial activity. Among the compounds tested, compounds 6.f, 7.g, 9.f and 10.f, 10 i were found to be most potent. The test compounds were found nontoxic upto the dose level of 2000 ${\mu}g$/mL. The intact compounds were then subjected for 3D-QSAR studies. 3D-QSAR study based on the principal of alignment of pharmacophoric features by Schrodinger PHASE module. The 3D-QSAR study allowed us to confirm the preferential binding mode of p-hydroxybenzohydrazide inside the active site.

• YAKHAK HOEJI
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• v.54 no.4
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• pp.288-294
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• 2010

Three dimensional quantitative-structure relationships (3D-QSARs) models between structures of phenoxy, phenylthio or benzyloxy substituted quinolone analogues and their antitrypanosomal activity against Chagas disease (Trypanosoma cruzi) were derived and discussed quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. The optimized CoMFA 1 model ($q^2$=0.528 and $r^2$=0.964) showed the best statistical results. According to the optimized CoMFA 1 model, the antitrypanosomal activities were dependent on the steric (60.0%) and electrostatic (36.2%) factors of quinolone derivatives. From the contour maps, it is predicted that the activity will be increased when sterically favored groups were located in $R_4$ and $R_5$ position and sterically disfavored groups were located in $R_2$ position. Also, the positively charged groups on $R_2$ would be able to increase the antitrypanosomal activities.

• Bulletin of the Korean Chemical Society
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• v.34 no.3
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• pp.837-850
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• 2013

Bovine viral diarrhea virus (BVDV), a major pathogen of cattle, is a well-characterized pestivirus which has been used as a good model virus for HCV. The RNA-dependent RNA polymerase (RdRp) plays a key role in the RNA replication process, thus it has been targeted for antivirus drugs. We employed two-dimensional quantitative structure-activity relationship (2D-QSAR) and molecular field analysis (MFA) to identify the molecular substructure requirements, and the particular characteristics resulted in increased inhibitory activity for the known series of compounds to act as effective BVDV inhibitors. The 2D-QSAR study provided the rationale concept for changes in the structure to have more potent analogs focused on the class of arylazoenamines, benzimidazoles, and acridine derivatives with an optimal subset of descriptors, which have significantly contributed to overall anti-BVDV activity. MFA represented the molecular patterns responsible for the actions of antiviral compound at their receptors. We conclude that the polarity and the polarizability of a molecule play a main role in the inhibitory activity of BVDV inhibitors in the QSAR modeling.