• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.441-447
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• 2010

B13, a ceramide analogue, is a ceramidase inhibitor and induces apoptosis to give potent anticancer activity. A series of thiourea B13 analogues was evaluated for their in vitro cytotoxic activities against human renal cancer Caki-2 and leukemic cancer HL-60 in the MTT assay. Some compounds (12, 15, and 16) showed stronger cytotoxicity than B13 and C6-ceramide against both tumor cell lines, and compound (12) gave the most potent activity with $IC_{50}$ values of 36 and $9\;{\mu}M$, respectively. Molecular modeling of thiourea B13 analogues was carried out by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). We obtained highly reliable and predictive CoMSIA models with cross-validated $q^2$ values of 0.707 and 0.753 and CoMSIA contour maps to show the structural requirements for potent activity. These data suggest that the amide group of B13 could be replaced by thiourea, that the stereochemistry of 1,3-propandiol may not be essential for activity and that long alkyl chains increase cytotoxicity.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.357.1-357.1
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• 2002

Three-dimensional quantitative activity relationship (3D-QSAR) study for a series of arylsulfonylimidazolidinone derivatives with antitumor activity was conducted using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices anaysis (CoMSIA). The in vitro cytotoxicity against human lung carcinoma (A549) exhibited a strong correlation with steric and electrostatic factors of the molecules. (omitted)

• Bulletin of the Korean Chemical Society
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• v.35 no.7
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• pp.2065-2071
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• 2014

${\beta}$-Secretase (beta-amyloid converting enzyme 1 [BACE1]) is involved in the first and rate-limiting step of ${\beta}$-amyloid ($A{\beta}$) peptides production, which leads to the pathogenesis of Alzheimer's disease(AD). Therefore, inhibition of BACE1 activity has become an efficient approach for the treatment of AD. Ligand-based and docking-based 3D-quantitative structure-activity relationship (3D-QSAR) studies of acyl guanidine analogues were performed with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) to obtain insights for designing novel potent BACE1 inhibitors. We obtained highly reliable and predictive CoMSIA models with a cross-validated $q^2$ value of 0.725 and a predictive coefficient $r{^2}_{pred}$ value of 0.956. CoMSIA contour maps showed the structural requirements for potent activity. 3D-QSAR analysis suggested that an acyl guanidine and an amide group in the $R_6$ substituent would be important moieties for potent activity. Moreover, the introduction of small hydrophobic groups in the phenyl ring and hydrogen bond donor groups in 3,5-dichlorophenyl ring could increase biological activity.

• Bulletin of the Korean Chemical Society
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• v.34 no.6
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• pp.1823-1828
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• 2013

Tetraoxanes (1,2,4,5-tetraoxanes) have been reported to exhibit potent antimalarial activity. In the present study, the three dimensional-quantitative structure activity relationship (3D-QSAR) studies were performed on a series of tetraoxanes derivatives using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. The best predictive CoMFA model with atom fit alignment resulted in cross-validated coefficient ($q^2$) value of 0.719, non-cross-validated coefficient ($r^2$) value of 0.855 with standard error of estimate (SEE) 0.335. Similarly, the best predictive CoMSIA model was derived with $q^2$ of 0.739, $r^2$ of 0.847 and SEE of 0.344. The generated models were externally validated using test sets. The final QSAR models as well as the information gathered from 3D contour maps should be useful for the design of novel tetraoxanes having improved antimalarial activity.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.511-516
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• 2009

A series of substituted 2-arylnaphthyridin-4-one analogues, which were previously synthesized in our laboratory, were evaluated for their in vitro cytotoxic activity against human lung cancer A549 and human renal cancer Caki-2 cells using MTT assay. Some compounds (11, 12, and 13) showed stronger cytotoxicity than colchicine against both tumor cell lines, and compound 13 exhibited the most potent activity with $IC_{50}$ values of 2.3 and $13.4\;{\mu}M$, respectively. Three-dimensional quantitative structure activity relationship (3D-QSAR) studies of comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed. Predictive 3D-QSAR models were obtained with $q^2$ values of 0.869 and 0.872 and $r^2_{ncv}$ values of 0.983 and 0.993 for CoMFA and CoMSIA, respectively. These results demonstrate that CoMFA and CoMSIA models could be reliably used in the design of novel cytotoxic agents.

• Bulletin of the Korean Chemical Society
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• v.25 no.10
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• pp.1513-1520
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• 2004

We investigate a series of synthesized ${\beta}$-methoxyacrylate analogues for their 3D QSAR & HQSAR against Magnaporthe grisea (Rice Blast Disease). We perform the three-dimensional Quantitative Structure-Activity Relationship (3D-QSAR) studies, using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) procedure. In addition, we carry out a two-dimensional Quantitative Structure-Activity Relationship (2D-QSAR) study, using the Hologram QSAR (HQSAR). We perform these studies, using 53 compounds as a training set and 10 compounds as a test set. The predictive QSAR models have conventional $r^2$ values of 0.955 at CoMFA, 0.917 at CoMSIA, and 0.910 at HQSAR respectively; similarly, we obtain cross-validated coefficient $q^2$ values of 0.822 at CoMFA, 0.763 at CoMSIA, and 0.816 at HQSAR, respectively. From these studies, the CoMFA model performs better than the CoMSIA model.

• YAKHAK HOEJI
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• v.55 no.2
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• pp.91-97
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• 2011

To search a new anti-depressant agents against para-chloroamphetamine-induced excitation, three dimensional quantitative-structure relationships (3D-QSAR) models between structure of 3a,4-dihydro-3H-[1]-benzopyronao[4,3]isoxazoles (1-30) and thieir inhibitory activity against para-chloroamphetamine-induced excitation were performed and discussed quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. From these basis on the findings, the optimized CoMSIA-2F model ($q^2$=0.793 and $r^2$=0.952) showed the best statistical results. And also, it is found that the para-chloroamphetamine inhibitory activity from the optimized CoMSIA-2F model was dependent on steric field (35.2%) and electrostatic field (64.8%) of tricyclic isoxazoles. Particularly, it is predicted that the inhibitory activity against para-chloroamphetamine-induced excitation will be able to increase by the designed compounds from the CoMSIA-2F model.

• Applied Biological Chemistry
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• v.48 no.3
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• pp.252-257
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• 2005

Three-dimensional quantitative structure-activity relationships (3D-QSARs) for the herbicidal activities against pre-emergence barnyard grass (Echinochloa crus-galli) by new 2-(4-(6-chloro-2-benzoxazolyloxy)phenoxy)-N-phenylpropion amide derivatives were studied quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methodologies. The best CoMFA model (AI-2) and CoMSIA model (AII-4) were derived from an atom based fit alignment and a combination of CoMFA fields. The herbicidal activities from CoMFA and CoMSIA contour maps showed that the activity will be able to be increased according to the substituents variation on the N-phenyl ring.

• Bulletin of the Korean Chemical Society
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• v.26 no.6
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• pp.952-958
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• 2005

Angiotensin-converting enzyme (ACE) is known to be primarily responsible for hypertension. Threedimensional quantitative structure-activity relationship (3D-QSAR) models have been constructed using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) for a series of 28 ACE inhibitors. The availability of ACE crystal structure (1UZF) provided the plausible biological orientation of inhibitors to ACE active site (C-domain). Alignment for CoMFA obtained by docking ligands to 1UZF protein using FlexX program showed better statistical model as compared to superposition of corresponding atoms. The statistical parameters indicate reasonable models for both CoMFA ($q^2$ = 0.530, $r^2$ = 0.998) and CoMSIA ($q^2$ = 0.518, $r^2$ = 0.990). The 3D-QSAR analyses provide valuable information for the design of ACE inhibitors with potent activity towards C-domain of ACE. The group substitutions involving the phenyl ring and carbon chain at the propionyl and sulfonyl moieties of captopril are essential for better activity against ACE.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2005.09a
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• pp.249-255
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• 2005

Angiotensin-converting enzyme (ACE) is primarily responsible for human hypertension. Current ACE drugs show serious cough and angiodema health problems due to the un-specific activity of the drug to ACE protein. The availability of ACE crystal structure (1UZF) provided the plausible biological orientation of inhibitors to ACE active site (C-domain). Three-dimensional quantitative structure-activity relationship (3D-QSAR) models have been constructed using the comparative molecula. field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) for a series of 28 ACE inhibitors. Alignment for CoMFA obtained by docking ligands to 1UZF protein using FlexX program showed better statistical model as compared to superposition of corresponding atoms. The statistical parameters indicate reasonable models for both CoMFA (q$^2$ = 0.530, r$^2$ = 0.998) and CoMSIA (q$^2$= 0.518, r$^2$ = 0.990). The 3D-QSAR analyses provide valuable information for the design of ACE inhibitors with potent activity towards C-domain of ACE. The group substitutions involving the phenyl ring and carbon chain at the propionyl and sulfonyl moieties of captopril are essential for specific activity to ACE.