Browse > Article

3D-QSAR Analysis on the Antitrypanosomal Activity of Phenoxy, Phenylthio or Benzyloxy Group Substituted Quinolone Analogues  

Myung, Pyung-Keun (Department of Pharmacy, College of Pharmacy, Chungnam National University)
Kang, Na-Na (Department of Pharmacy, College of Pharmacy, Chungnam National University)
Kim, Sang-Jin (Department of Cosmetic Science, Daejeon Health Sciences College)
Sung, Nack-Do (Department of Applied Biological Chemistry, College of Agriculture & Life Science, Chungnam National University)
Publication Information
YAKHAK HOEJI / v.54, no.4, 2010 , pp. 288-294 More about this Journal
Abstract
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.
Keywords
antitrypanosomal activity; Chagas disease; CoMFA; 3D-QSAR; quinolone analogues;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Otero, L., Aguirre, G., Boiani, L., Denicola, A., Rigol, C., Olea-Azar, C., Maya, J. D., Morello, A., Gonzalez, M., Gambino, D. and Cerecetto, H. : Nitrofurylsemicarbazone rhenium and ruthenium complexes as anti-trypanosomal agents. E. J. Med. Chem. 41, 1231 (2006).   DOI   ScienceOn
2 James, M. K., Christophe, L. M. J. V., Mandana, K., Galina, I. L., Michael, H. G. and Frederick, S. B. : Rational modification of a candidate cancer drug for use against chagas disease. J. Med. Chem. 52, 1639 (2009).   DOI   ScienceOn
3 Appelbaum, P. C. and Hunter, P. A. : The fluoroquinolone antibacterials: past, present and future perspectives. I. J. Antimicrobial Agents 16, 5 (2000).   DOI   ScienceOn
4 Rodrigues, C., Batista, A. A., Aucelio, R. Q., Teixeira, L. R., Visentin, L. D. C. and Beraldo, H. : Spectral and electrochemical studies of ruthenium (II) complexes with $N^4$-methyl- 4-nitrobenzaldehyde and $N^4$-methyl-4-nitrobenzophenone thiosemicarbazone: Potential anti-trypanosomal agents. Polyhedron 27, 3061 (2008).   DOI   ScienceOn
5 Belal, F., Al-Majed, A. A. and Al-Obaid, A. M. : Methods of analysis of 4-quinolone antibacterials. Talanta 50, 765 (1999).   DOI   ScienceOn
6 Zafra-Gmez, A., Garballo, A., Ballesteros, O., Navaln, A. and Garca-Ayuso, L. E. : Simultaneous determination of quinolone antibacterials in bovine milk by liquid chromatography - mass spectrometry. Biomed. Chromatogr. 22, 1186 (2008).   DOI   ScienceOn
7 Iztok, T. : The interactions of metal ions with quinolone antibacterial agents. Coordination Chem. 232, 27 (2002).   DOI   ScienceOn
8 Xiang, M., Weicheng, Z. and Reto, B. : Synthesis, in vitro antitrypanosomal and antibacterial activity of phenoxy, phenylthio or benzyloxy substituted quinolones. Bio. Med. Chem. 19, 986 (2009).   DOI   ScienceOn
9 Cramer, R. D. III, Patterson, D. E. and Bunce, J. D. : Comparative molecular field analysis (CoMFA), 1. Effect of shape on the binding of steroid to carrier proteins. J. Am. Chem. Soc. 110, 5959 (1988).   DOI   ScienceOn
10 Klebe, G., Abraham, U. and Mietzner, T. : Molecular similarity indexes in a comparativeanalysis (comsia) of drug molecules to correlate and predict their biological-activity. J. Med. Chem. 37, 4130 (1994).   DOI   ScienceOn
11 Juan, M. B., Maria, S. P., Hector, W. R., Alicia, R. F., Julio, E. E., Ricardo, E. F. and Patricia, P. O. : Treatment with benznidazole or thioridazine in the chronic phase of experimental Chagas disease improves cardiopathy. Int. J. Parasitol. 29, 733 (2007).
12 Juan, M. B., He'ctor, W. R., Alicia, R. F. and Julio, E. E. : Trypanosoma cruzi reinfections in mice determine the severity of cardiac damage. Int. J. Parasitol. 32, 889 (2002).   DOI   ScienceOn
13 Castro, J. A., Montalto de Mecca, M. and Bartel, L. C. : Toxic side effects of drugs used to treat Chagas disease (American trypanosomiasis). Hum. Exp. Toxicol. 25, 471 (2006).   DOI   ScienceOn
14 Silva, J. J. N., Pavanelli, W. R., Gutierrez, S. F. R., Lima, F. C. A., Silva, A. B. F., Silva, J. S. and Franco, D. W. : Complexation of the anti-Trypanosoma cruzi drug benznidazole improves solubility and efficacy. J. Med. Chem. 51, 4104 (2008).   DOI   ScienceOn
15 Poli, P., Michele, A. M., Annamaria, B., Renato, A. M., Cristina, N. A., Solange, S. Carlo, R. and Tania Maria, A. D. Z. : Cytotoxic and genotoxic effects of megazol, an anti-Chagas disease drug, assessed by different short-term tests. Biochem. 64, 1617 (2002).
16 Oliver, H., Michael, H. G., Christophe, L. M. J. V. and Frederick, S. B. : The protein farnesyltransferase inhibitor tipifarnib as a new lead for the development of drugs against chagas disease. J. Med. Chem. 48, 5415 (2005).   DOI   ScienceOn
17 Shimoda, K. : Mechanisms of quinolone phototoxicity. Toxicology Letters 102-103, 369 (1998).   DOI   ScienceOn
18 Demir, O. and Roitberg, A. E. : Modulation of catalytic function by differential plasticity of the active site: case study of Trypanosoma cruzi trans-sialidase and Trypanosoma rangeli sialidase. Biochem. 48, 3398 (2009).   DOI   ScienceOn
19 Lesher, G. Y., Froelich, E. J., Gruet, M. D., Bailey, J. H. and Brundage, R. P. : 1,8-Naphthyridine derivatives. A new class of chemotherapeutic agents. J. Med. Chem. 5, 1063 (1962).   DOI   ScienceOn
20 Herna'ndez-Arteseros, J. A., Barbosa., J., Compano, R. and Prat, M. D. : Analysis of quinolone residues in edible animal products. J. Chromatography A. 945, 1 (2002).   DOI   ScienceOn
21 Rodigues, P. R., Lane, J. E., Carter, C. E., Bogitsh, B. J., Singh, P. K., Zimmerman, L. J., Molenda, J. J. and Jones, M. M. : Chelating agent inhibition of Trypanosoma cruzi epimastigotes in vitro. J. Inorganic Biochem. 60, 277 (1995).   DOI   ScienceOn
22 Choe, Y. C., Brinen, L. S., Price, M. S., Engel, J. C., Lange, M., Grisostomi, C., Weston, S. G., Pallai, P. V., Cheng, H., Hardy, L. W., Hartsough, D. S., McMakin, M., Tilton, R. F., Baldinod, C. M. and Craika, C. S. : Development of $\alpha$-keto-based inhibitors of cruzain, a cysteine protease implicated in Chagas disease. Bioorganic Med. Chem. 13, 2141 (2005).   DOI   ScienceOn
23 Caetano, L. C., Braza, V., Filipin, M. D. V., Santello, F. H., Caetano, L. N., Toldo, M. P. A., Caldeira, J. C. and Jr. Prado, J. C. D. : Effects of repetitive stress during the acute phase of Trypanosoma cruzi infection on chronic Chagas disease in rats. Stress 12, 144 (2009).   DOI   ScienceOn
24 Otero, L., Vieites, M., Boiani, L., Denicola, A., Rigol, C., Opazo, L., Olea-Azar, C., Maya, J. D., Morello, A., Krauth-siegel, R. L., Piro, O. E., Castellano, E., Gonzalez, M., Gambino, D. and Cerecetto, H. : Novel antitrypanosomal agents based on palladium nitrofurylthiosemicarbazone complexes: DNA and redox metabolism as potential therapeutic targets. J. Med. Chem. 49, 3322 (2006).   DOI   ScienceOn
25 Wold, S., Johansson, E. and Cocchi, M. : PLS-partial least squares projections to latent structures, in 3D-QSAR in Drug Design: Theory, Methods and Applications (ed. H. Kubinyi), ESCOM, Leiden, pp. 523-550 (1993).
26 Oliveira, E. C., Stefani, M. M. A., Campos, D. E., Andrade, A. L. S. S., Silva, S. A., Rassi, A. and Luquetti, A. O. : Trypanosoma cruzi stocks isolated from acute Chagas disease patients lead to lethal murine infection. Transactions of the Royal Society of Tropical Medicine and Hygiene 91, 25 (1997).   DOI   ScienceOn
27 Ricardo, P. F., Maria del carmen, S. G., Carlos, G. A., Monteo'n, V. M., Reyes, P. A. and Rosales-encina, J. L. : Humoral nitric oxide levels and antibody immune response of symptomatic and indeterminate chagas disease patients to commercial and autochthonous Trypanosoma cruzi antigen. Am. J. Trop. Med. Hyg. 58, 715 (1998).   DOI
28 Mezencev, R., Galizzi, M., Kutschy, P. and Docampo, R. : Trypanosoma cruzi: Antiproliferative effect of indole phytoalexins on intracellular amastigotes in vitro. Exp. Parasitol. 122, 66 (2009).   DOI   ScienceOn
29 Soung, M. K., Lee, Y. J. and Sung, N. D. : 3D-QSARs of herbicidal 2-N-phenylisoindolin-1-one analogues as a new class of potent inhibitors of protox. Bull. Kor. Chem. Soc. 30, 613 (2009).   DOI   ScienceOn
30 Vasan, A. and Komaragiri, S. R. : Comparative analysis of simulated annealing, simulated quenching and genetic algorithms for optimal reservoir operation. Applied Soft Computing 9, 274 (2009)   DOI   ScienceOn