• Title, Summary, Keyword: comparative molecular similarity indices analysis (CoMSIA)

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Comparison of QSAR Methods (CoMFA, CoMSIA, HQSAR) of Anticancer 1-N-Substituted Imidazoquinoline-4,9-dione Derivatives

  • Suh, Myung-Eun;Park, So-Young;Lee, Hyun-Jung
    • Bulletin of the Korean Chemical Society
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    • v.23 no.3
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    • pp.417-422
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    • 2002
  • Comparison studies of the Quantitative Structure Activity Relationship (QSAR) methods with new imidazo-quinolinedione derivatives were conducted using Comparative Molecular Field Analysis (CoMFA), Comparative Molecular Similarity Indices Analysis (CoMSIA), and the Hologram Quantitative Structure Activity Relationship (HQSAR). When the CoMFA crossvalidation value, q2, was 0.625, the Pearson correlation coefficient, r2, was 0.973. In CoMSIA, q2 was 0.52 and r2 was 0.979. In the HQSAR, q2 was 0.501 and r2 was 0.924. The best result was obtained using the CoMSIA method according to a comparison of the calculated values with the real in vitro cytotoxic activities against human ovarian cancer cell lines.

Molecular Docking, 3D QSAR and Designing of New Quinazolinone Analogues as DHFR Inhibitors

  • Yamini, L.;Kumari, K. Meena;Vijjulatha, M.
    • Bulletin of the Korean Chemical Society
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    • v.32 no.7
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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.

Comparative Molecular Similarity Indices Analysis (CoMSIA) of 8-substituted-2-aryl-5-alkylaminoquinolines as Corticotropin-releasing factor-1 Receptor Antagonists

  • Nagarajan, Santhosh Kumar;Madhavan, Thirumurthy
    • Journal of the Chosun Natural Science
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    • v.9 no.4
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    • pp.241-248
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    • 2016
  • Corticotropin-releasing factor receptors (CRFRs) activate the hypothalamic-pituitary-adrenal axis, which is an integral part of the fight or flight response to stress. Increase in CRH level is observed in Alzheimer's disease and major depression and hypoglycemia. Here, we report on the relevant physicochemical parameters required for the CRFR inhibitors. Comparative molecular similarity indices analysis (CoMSIA) was performed with the derivatives of 8-substituted-2-aryl-5-alkylaminoquinolinesas CRFR inhibitors. The best predictions were obtained for the best CoMSIA model with a $q^2$ of 0.576 with 6 components and $r^2$ of 0.977. The statistical parameters from the generated CoMSIA models indicated that the data are well fitted and have high predictive ability. CoMSIA contour maps could be useful in the designing of more potent and novel CRFR derivatives.

Development of new agrochemicals by quantitative structure-activity relationship (QSAR) methodology. III. 3D QSAR methodologies and computer-assisted molecular design (CAMD) (정량적인 구조-활성상관 (QSAR) 기법에 의한 새로운 농약의 개발. III. 3D QSAR 기법들과 컴퓨터를 이용한 분자설계(CAMD))

  • Sung, Nack-Do
    • The Korean Journal of Pesticide Science
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    • v.7 no.1
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    • pp.1-11
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    • 2003
  • Acoording to improvement of HTOS (high throughput organic synthesis) and HTS (high throughput screening) technique, the CoMFA (comparative molecular field analysis), CoMSIA (comparative molecular similarity indeces analysis) and molecular HQSAR (hologram quantitative structure-activity relationship) analysis techniques as methodology of computer assisted molecular design (CAMD) were introduced generally and summarized for some application cases.

CoMFA and CoMSIA 3D QSAR Studies on Pimarane Cyclooxygenase-2 (COX-2) Inhibitors

  • Suh, Young-Ger;Lee, Kwang-Ok;Park, Hyun-Ju;Kim, Young-Ho;Moon, Sung-Hyun
    • Proceedings of the PSK Conference
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    • pp.250.1-250
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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)

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Comparative Molecular Similarity Indices Analysis (CoMSIA) on the Melanogenesis Inhibitory Activities of Alkyl-3,4-dihydroxy- benzoate and N-alkyl-3,4-dihydroxybenzamide Derivatives.

  • Kim, Sang-Jin;Sung, Nack-Do;Lee, Sang-Ho
    • Proceedings of the SCSK Conference
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    • pp.733-740
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    • 2003
  • To find a new substance with superior melanogenesis inhibitory activity, the bioactivities of alkyl-3,4-dihydroxy-5-substituted benzoate (A) and N-alkyl-3,4-dihydroxy-5-substituted benzamide (B) derivatives as substrate of tyrosinase were measured in mouse melanoma cells. And the bioactivities analyzed using comparative molecular similarity indices analysis (CoMSIA). From the CoMSIA model, when cross-validation value (q$^2$) is 0.713 at four components, the pearson correlation coefficient ($r^2$) is 0.900. Unknown compounds were predicted, using QSAR analyzed results from the CoMSIA methods. Excellent agreement was obtained between the measured and the predicted bioactivities of unknown compounds. As the results of prediction from CoMSIA, we could conclude that the bioactivities were increased from pl$_{50}$=3.18-4.80 to above 5.17 by creation of 6-methylheptyl, n-pentylphenyl and 2-hydroxypentylphenyl group etc,.,.

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Comparative Molecular Similarity Indices Analysis of Caspase-3 Inhibitors

  • Babu, Sathya;Madhavan, Thirumurthy
    • Journal of the Chosun Natural Science
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    • v.7 no.4
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    • pp.227-233
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    • 2014
  • Caspases, a family of cysteinyl aspartate-specific proteases plays a central role in the regulation and the execution of apoptotic cell death. Activation of caspases-3 stimulates a signaling pathway that ultimately leads to the death of the cell. Hence, caspase-3 has been proven to be an effective target for reducing the amount of cellular and tissue damage. In this work, comparative molecular similarity indices analysis (CoMSIA) was performed on a series of 3,4-dihydropyrimidoindolones derivatives which are inhibitors of caspase-3. The best predictions were obtained for CoMSIA model ($q^2$ = 0.586, $r^2$ = 0.955). The predictive ability of test set ($r^2_{pred}$) was 0.723. Statistical parameters from the generated QSAR models indicated the data is well fitted and have high predictive ability. Our theoretical results could be useful to design novel and more potent caspase-3 derivatives.

3D-QSAR Analysis and Molecular Docking of Thiosemicarbazone Analogues as a Potent Tyrosinase Inhibitor

  • Park, Joon-Ho;Sung, Nack-Do
    • Bulletin of the Korean Chemical Society
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    • v.32 no.4
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    • pp.1241-1248
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    • 2011
  • Three dimensional quantitative structure-activity relationships (3D-QSARs) between new thiosemicarbazone analogues (1-31) as a substrate molecule and their inhibitory activity against tyrosinase as a receptor were performed and discussed quantitatively using CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) methods. According to the optimized CoMSIA 2 model obtained from the above procedure, inhibitory activities were mainly dependent upon H-bond acceptor favored field (36.5%) of substrate molecules. The optimized CoMSIA 2 model, with the sensitivity of the perturbation and the prediction, produced by a progressive scrambling analysis was not dependent on chance correlation. From molecular docking studies, it is supposed that the inhibitory activation of the substrate molecules against tyrosinase (PDB code: 1WX2) would not take place via uncompetitive inhibition forming a chelate between copper atoms in the active site of tyrosinase and thiosemicarbazone moieties of the substrate molecules, but via competitive inhibition based on H-bonding.

3D-QSAR (CoMFA, CoMSIA) study of PPAR-$\gamma$ agonists.

  • Lee, Hye-Sun;Chae, Chong-Hak;Yoo, Sung-Eun;Yi, Kyu-Yang;Park, Kyung-Lae
    • Proceedings of the PSK Conference
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    • pp.181.3-181
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    • 2003
  • Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on 60 PPAR-g agonists. Partial Least Squars (PLS) analysis produced good predicted models with $q^2$ value of 0.62 (SDEP=0.33, F value=93.22, $r^2$=0.92) and 0.56 (SDEP=0.47 F value=27.65, $r^2$=0.86), respectivly. The key spatial properties were detected by careful analysis of the isocontour maps.

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Pharmacophore-Based Comparative Molecular Similarity Indices Analysis of CRTh2 Antagonists

  • Babu, Sathya
    • Journal of the Chosun Natural Science
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    • v.8 no.4
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    • pp.273-284
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    • 2015
  • Chemoattractant Receptor Homologous molecule expressed on Th2 cells (CRTh2) is a chemoattractant receptor with seven transmembrane helices targeted for inflammatory diseases such as asthma and allergic rhinitis. In this study, pharmacophore based Comparative Molecular Similarity Indices Analysis (CoMSIA) were performed on the series of 2-(2-(benzylthio)-1H-benzo[d]imidazol-1-yl) acetic acids derivatives. Initially, GASP module was used for generation of pharmacophore models using five highly active compounds from the dataset. Among the generated pharmacophores, the best pharmacophore model was selected based on fitness score and was used as template for the alignment of compounds which was used for CoMSIA analysis. The best predictions were obtained utilizing steric, hydrophobic and H-bond acceptor parameters showing a $q^2$=0.559 and $r^2$=0.730. 15 test set compounds was used to investigate the predictive ability of the CoMSIA model. Contour maps suggested that presence of bulky substituents and H-bond acceptor atoms at $5^{th}$ position of benzene ring will increase the activity of the compounds. The results obtained from this study will be useful to design more potent CRTh2 antagonists.