• Bulletin of the Korean Chemical Society
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• 제27권2호
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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.

• Bulletin of the Korean Chemical Society
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• 제35권7호
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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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• 제32권7호
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• pp.2433-2442
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• 2011

The three dimensional quantitative structure activity relationship (3D QSAR) models were developed using Comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA) and docking studies. The fit of Quinazolinone antifolates inside the active site of modeled bovine dihydrofolate reductase (DHFR) was assessed. Both ligand based (LB) and receptor based (RB) QSAR models were generated, these models showed good internal and external statistical reliability that is evident from the $q^2_{loo}$, $r^2_{ncv}$ and $r^2_{pred}$. The identified key features enabled us to design new Quinazolinone analogues as DHFR inhibitors. This study is a building bridge between docking studies of homology modeled bovine DHFR protein as well as ligand and target based 3D QSAR techniques of CoMFA and CoMSIA approaches.

• 약학회지
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• 제58권1호
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• pp.53-57
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• 2014

In recent, the abuse of newly-emerging psychoactive drugs, ('designer drugs') is a rapidly increasing problem in Korean society. Quantitative-structure activity relationship (QSAR) is an alternative method to predict bioactivities of new abused compounds. In this study, cathinone-related new designer drugs, 4-methylbuphedrone and 4-methoxy-N,N-dimethylcathinone were tested for prediction of the bioactivity with QSAR model. The bioactivity of 4-methylbuphedrone and 4-methoxy-N,N-dimethylcathinone was similar to those of methylone. These results suggest that the prediction with QSAR model may provide scientific evidences for regulatory decision.

• The Korean Journal of Physiology and Pharmacology
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• 제13권6호
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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.

• 통합자연과학논문집
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• 제10권3호
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• pp.141-147
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• 2017

Vascular endothelial growth factor (VEGF) is an important signaling protein involved in angiogenesis, which is the formation of new blood vessels from pre-existing vessels. Consequently, blocking of the vascular endothelial growth factor receptor (VEGFR-2) by small molecule inhibitors leads to the inhibition of cancer induced angiogenesis. In this study, we performed a two dimensional quantitative structure activity relationship (2D-QSAR) study of 38 N-Phenyl-N'-{4-(4-quinolyloxy) phenyl} urea derivatives as VEGFR-2 inhibitors based on hologram quantitative structure-activity (HQSAR). The model developed showed reasonable $q^2=0.521$ and $r^2=0.932$ values indicating good predictive ability and reliability. The atomic contribution map analysis of most active compound (compound 7) indicates that hydrogen and oxygen atoms in the side chain of ring A and oxygen atom in side chain of ring C contributes positively to the activity of the compounds. The HQSAR model developed and the atomic contribution map can serve as a guideline in designing new compounds for VEGFR-2 inhibition.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.356.2-356.2
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• 2002

The structure of 1-phenyl-2-substituted thiourea derivatives have been studied and optimized for their cytotoxic activity. The three dimensional quantitative structure activity relationship (3D-QSAR) was investigated using comparative molecular field analysis (CoMFA). The result suggested that electrostatic and steric factors of 2-alkylureido-1-phenyl propanol derivatives were correlated well with cytotoxic activity. (omitted)

• 통합자연과학논문집
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• 제4권3호
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• pp.210-215
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• 2011

Holographic quantitative structure-activity relationships (HQSAR) is a useful tool to correlates structures with their biological activities. HQSAR is a two dimensional (2D) QSAR methodology, which generates QSAR equations through 2D fingerprint and correlates it with biological activity. Here, we report a 2D-QSAR model for a series of fifty-one 3,4-dihydroxychalcones derivatives utilizing HQSAR methodology. We developed HQSAR model with 6 optimum numbers of components (ONC), which resulted in cross-validated correlation coefficient ($q^2$) of 0.855 with 0.283 standard error of estimate (SEE). The non-cross-validated correlation coefficient (r2) with 0.966 indicates the model is predictive enough for analysis. Developed HQSAR model was binned in to a hologram length of 257. Atomic contribution map revealed the importance of dihydroxy substitution on phenyl ring.

• Bulletin of the Korean Chemical Society
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• 제25권10호
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제17권3호
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• pp.237-243
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• 2013

B13 is a ceramide analogue and apoptosis inducer with potent cytotoxic activity. A series of arylpropyl sulfonamide analogues of B13 were evaluated for their cytotoxicity using MTT assays in prostate cancer PC-3 and leukemia HL-60 cell lines. Some compounds (4, 9, 13, 14, 15, and 20) showed stronger activities than B13 in both tumor cell lines, and compound (15) gave the most potent activity with $IC_{50}$ values of 29.2 and 20.7 ${\mu}M$, for PC-3and HL-60 cells, respectively. Three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was performed to build highly reliable and predictive CoMSIA models with cross-validated $q^2$ values of 0.816 and 0.702, respectively. Our results suggest that long alkyl chains and a 1R, 2R configuration of the propyl group are important for the cytotoxic activities of arylpropyl sulfonamides. Moreover, the introduction of small hydrophobic groups in the phenyl ring and sulfonamide group could increase biological activity.