• 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.

• Reproductive and Developmental Biology
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• v.34 no.1
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• pp.7-13
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• 2010

The binding affinity constants ($p(Od)_{50}$) and molecular docking scores (OS) between porcine odorant binding proteins pOBP (1HQP) and pPBP (1GM6) as receptor and a series of tetrahydrofuran-2-yl (A & B) analogues as substrate, and their interactions were discussed quantitatively using three-dimensional quantitative structure-activity relationship (30-QSAR) models. The statistical qualities of the optimized CoMF A models for pOBP were better than those of the CoMSIA models. The binding affinity constants and OS between substrate and receptor molecules were dependent upon steric and hydrophobic interaction. The DS constants of the substrates into the binding site of OBP (1HQP) were bigger than those of PBP (1GM6). The resulting contour maps produced by the optimized CoMFA model were used to identify the structural features relevant to the binding affinity in binding site of pOBP.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.3
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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.

• Reproductive and Developmental Biology
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• v.32 no.3
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• pp.141-146
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• 2008

To search a new porcine pheromonal odorant, the models of four type (2D-QSAR, HQSAR, CoMFA & CoMSlA) were derived from quantitative structure-activity relationship (QSAR) between tetrahydrofuran-2-yl family compounds and their observed binding affinity constants (Obs.p$[Od]_{50}$). The optimized CoMFA model (predictability; $r^{2}_{cv.}(q^2)$=0.886 & correlation coefficient: $r^{2}_{ncv.}$=0.984) from ligand based approaches was confirmed as the best model among them. The $N^{1}$-allyl-$N^{2}$-(tetrahydrofuran-2-yl)methyl)oxalamide (P1), 2-(4-trimethylammoniummethylcyclohexyloxy)tetrahydrofurane (P5) and 2-(3-trimethylammoniummethylcyclohexyloxy)tetrahydrofurane (P6) molecules predicted as porcine pheromonal odorant by the CoMFA model were showed relatively high binding affinity constant values (Pred.p$[Od]_{50}=8{\sim}10$) and very lower toxicity values against some sorts of toxicity.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.6
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• pp.517-523
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• 2013

Naphthyridine compounds are important, because they exhibit various biological activities including anticancer, antimicrobial, and anti-inflammatory activity. Some naphthyridines have antimitotic effects or demonstrate anticancer activity by inhibiting topoisomerase II. These compounds have been investigated as potential anticancer agents, and several compounds are now part of clinical trials. A series of naphthyridine derivatives were evaluated for their in vitro cytotoxic activities against human cervical cancer (HeLa), leukemia (HL-60), and prostate cancer (PC-3) cell lines using an MTT assay. Some compounds (14, 15, and 16) were more potent than colchicine against all three human cancer cell lines and compound (16) demonstrated potency with $IC_{50}$ values of 0.7, 0.1, and $5.1{\mu}M$, respectively. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used for quantitative structure-activity relationship (QSAR) molecular modeling of these compounds. We obtained accurate and predictive three-dimensional QSAR (3D-QSAR) models as indicated by the high PLS parameters of the HeLa ($q^2$, 0.857; $r^2$, 0.984; $r^2\;_{pred}$, 0.966), HL-60 ($q^2$, 0.777; $q^2$, 0.937; $r^2\;_{pred}$, 0.913), and PC-3 ($q^2$, 0.702; $q^2$, 0.983; $r^2\;_{pred}$, 0.974) cell lines. The 3D-QSAR contour maps suggested that the C-1 NH and C-4 carbonyl group of the naphthyridine ring and the C-2 naphthyl ring were important for cytotoxicity in all three human cancer cell lines.