Browse > Article

3D QSAR Studies on Cinnamaldehyde Analogues as Farnesyl Protein Transferase Inhibitors  

Nack-Do, Sung (Division of Applied Biology & Chemistry, College of Agricultural & Life Sciences, Chungnam National University)
Cho, Young-Kwon (Division of Applied Biology & Chemistry, College of Agricultural & Life Sciences, Chungnam National University)
Kwon, Byoung-Mog (Korea and Anti-biotic Material RU, Korea Research Institute of Bioscience and Biotechnology)
Hyun, Kwan-Hoon (Department of Chemistry, Inha University)
Kim, Chang-Kyung (Department of Chemistry, Inha University)
Publication Information
Archives of Pharmacal Research / v.27, no.10, 2004 , pp. 1001-1008 More about this Journal
Abstract
Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies on 59 cinnamaldehyde analogues as Farnesyl Protein Transferase (FPTase) inhibitors were investigated using comparative molecular field analysis (CoMFA) with the PLS region-focusing method. Forty-nine training set inhibitors were used for CoMFA with two different grid spacings, $2{\AA}\;and\;1{\AA}$ Ten compounds, which were not used in model generation, were used to validate the CoMFA models. After the PLS analysis, the best predictive CoMFA model showed that the cross-validated value $(r^2_{cv})$ and the non-cross validated conventional value$(r^2_{ncv})$ are 0.557 and 0.950, respectively. From the CoMFA contour maps, the steric and electrostatic properties of cinnamaldehyde analogues can be identified and verified.
Keywords
3D-QSAR; CoMFA; Cinnamaldehyde inhibitors; Farnesyl protein transterase;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
Times Cited By Web Of Science : 3  (Related Records In Web of Science)
Times Cited By SCOPUS : 3
연도 인용수 순위
1 Knight, D. W., Feverfew: chemistry and biological activity. Nat. Prod. Rep., 12,271-276 (1995)   DOI   PUBMED   ScienceOn
2 Kwon, B. M., Cho, Y. K., and Lee, S. H., 2'-Hydroxycinnamaldehyde from stem bark of Cinnamomum cassia. Planta Medica, 62,183-184 (1996)   DOI   PUBMED
3 Lindgren F, Geladi P, Rannar S, and Wold S., Interactive Variable Selection (Ivs) For Pis .1. Theory and Algorithms. J. Chemometr., 8, 349-363 (1994)   DOI   ScienceOn
4 Qian, Y., Blaskovich, M. A., Saleem, M., Seong, C. M., Wathen, S. P., Hamilton, A. D., and Sebti, S. M., Design and structural requirements of potent peptidomimetic inhibitors of p21ras famesyltransferase, J. Biol. Chem., 269,12410-12413 (1994)   PUBMED
5 Sung, N.-D., Cheun, Y. G., Kwon, B.-M., Park, H.-Y., and Kim, C. K., Modeling of inhibition mechanism of natural ligands to famesyl protein transferase using molecular docking. Bull. Kor. Chem. Soc., 24,1509-1511 (2003)   DOI
6 Zhu, L., Hou, T., and Xu, X., Three-dimensional quantitative structure-activity relationship study on paullones as CDK inhibitors using CoMSIA and CoMFA. J. Mol. Model., 7, 223-230 (2001)   DOI
7 Gibbs, J. B. and Oliff A., Pharmaceutical research in molecular oncology. Cell, 79,193-198 (1994)   DOI   ScienceOn
8 Podlogar, B. L., Muegge, I., and Brice, L. J., Computational methods to estimate drug development parameters. Curr. Opin. Drug Discovery Dev., 4,102-109 (2001)   PUBMED
9 Raichurkar, A. V. and Kulkarni, V. M., Understanding the antitumor activity of novel hydroxysemicarbazide derivatives as ribonucleotide reductase inhibitors using CoMFA and CoMSIA. J. Med.Chem., 46, 4419-4427 (2003)   DOI   ScienceOn
10 Schweins, T., Geyer, M., Scheffzek, K., Warshel, A., Kalbitzer, H. R., and Witlinghofer, A., Substrate-assisted catalysis as a mechanism for GTP hydrolysis of p21ras and other GTPbinding proteins. Nat. Struct. Biol., 2, 36-44 (1995)   DOI   ScienceOn
11 Wu, T.-S., Qu, L.-F., and Teng, C.-M., Aristolochic acids, aristolactam alkaloids and amides from Aristolochia kankauensis. Phytochemistry, 36,1063-1068 (1994)   DOI   ScienceOn
12 Choo, H.-Y. P., Choi, S., Ryu, C.-K., Kim, H.-J., Lee, I. Y., Pae, A. N., and Koh, H. Y., QSAR study of quinolinediones with inhibitory activity of endothelium-dependent vasorelaxation by CoMSIA. Bioorg. Med. Chem., 11,2019-2023 (2003)   DOI   ScienceOn
13 Cho, Y. K., CoMFA on Cinnamaldehyde Analogues against FPTase Inhibitory Acitivity, Ph.D. thesis, Graduate school of Chungnam National University, Korea (2002)
14 Reiss, Y., Goldstein J. L., Seabra, M. C., Casey, P.J., and Brown, M. S., Inhibition of purified $p21^{ras}$ farnesyl:protein transferase by Cys-AAX tetrapeptides. Cell, 62, 81-88 (1990)   DOI   ScienceOn
15 Kwon, B. M., Lee, S. H., Cho, Y. K., Bok, S. H., So, S. H., Youn, M. R., and Chang, S. I., Synthesis and biological activity of cinnamaldehyde as angiogenesis inhibitors. Bioorg. Med. Chem. Lett., 7, 2473-2476 (1997)   DOI   ScienceOn
16 Lodish, H., Berk, A., Zipursky, S. L., Matsudaira, P., Baltimore, D., and Darnell, J., Molecular Cell Biology, W. H. Freeman and Company, New York, (1995)
17 Cho, S. J., Garsia, M. L. S., Bier, J., and Tropsha, A., Structurebased alignment and comparative molecular field analysis of acetylcholinesterase inhibitors. J. Med. Chem., 39, 5064-5071 (1996)   DOI   ScienceOn
18 Adari, H., Lowy, D. R., Willumsen, B. M., Der, C. J., and McCormick, F., Guanosine triphosphate activating protein (GAP) interacts with the p21 ras effector binding domain. Science, 240, 518-521 (1988)   DOI   PUBMED
19 Huang, M., Yang, D.-Y., Shang, Z., Zou, J., and Yu, Q., 3DQSAR studies on 4-hydroxyphenylpyruvate dioxygenase inhibitors by comparative molecular field analysis (CoMFA). Bioorg. Med. Chem. Lett., 12,2271-2275 (2002)   DOI   ScienceOn
20 Pedretti, A., Villa, L., and Vistoli, G., Modeling of binding modes and inhibition mechanism of some natural ligands of farnesyl transferase using molecular docking. J. Med. Chem., 45, 1460-1465 (2002)   DOI   ScienceOn
21 Forina, M., Casolino, C., and Millan, C. P., Iterative predictor weighting (IPW) PLS: a technique for the elimination of useless predictors in regression problems. J. Chemometr, 13,165-184 (1999)   DOI   ScienceOn
22 Kwon, B. M., Lee, S. H., Choi, S. U., Park, S. H., Lee, C. O., Cho, Y. K., Sung, N. D., and Bok, S. H., Synthesis and in vitro cytotoxicity of cinnamaldehyde to human solid tumor cells. Arch. Pharm. Res., 21,147-152 (1998)   DOI   ScienceOn