Application of molecular topology to the prediction of inhibition of Trypanosoma cruzi Hexokinase by bisphosphonates

Authors

  • R GARCÍA-DOMENECH Dept. Química Física, Facultad de Farmacia, Universitat de Valencia, Avd. V.A. Estellés, s/n, 46100-Burjassot, Valencia, Spain
  • N ESPINOZA Dept. Química Física, Facultad de Farmacia, Universitat de Valencia, Avd. V.A. Estellés, s/n, 46100-Burjassot, Valencia, Spain
  • RF GALARZA Dept. Química Física, Facultad de Farmacia, Universitat de Valencia, Avd. V.A. Estellés, s/n, 46100-Burjassot, Valencia, Spain
  • MJ MORENO-PADILLA Dept. Química Física, Facultad de Farmacia, Universitat de Valencia, Avd. V.A. Estellés, s/n, 46100-Burjassot, Valencia, Spain
  • B ROJAS-RUIZ Dept. Química Física, Facultad de Farmacia, Universitat de Valencia, Avd. V.A. Estellés, s/n, 46100-Burjassot, Valencia, Spain
  • LL ROLDAN-ARROYO Dept. Química Física, Facultad de Farmacia, Universitat de Valencia, Avd. V.A. Estellés, s/n, 46100-Burjassot, Valencia, Spain
  • MI SANCHEZ-LAVADO Dept. Química Física, Facultad de Farmacia, Universitat de Valencia, Avd. V.A. Estellés, s/n, 46100-Burjassot, Valencia, Spain
  • J GÁLVEZ Dept. Química Física, Facultad de Farmacia, Universitat de Valencia, Avd. V.A. Estellés, s/n, 46100-Burjassot, Valencia, Spain

Keywords:

Molecular topology, Trypanosoma cruzi hexokinase, Linear discriminant analysis, Virtual screening

Abstract

A topological-mathematical model has been arranged to search for new derivatives of bisphosphonate compounds actingas inhibitors against Trypanosoma cruzi hexokinase. By using linear discriminant analysis, a four-variable function wasachieved allowing an accurate prediction of the IC50 for each compound of the training and test series. After carryingout a virtual screening based upon such a model, new structures potentially actives against T. cruzi are proposed

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References

Organization WH. Burdens and Trends in Chagas disease. [cited]; Available from: www.who.int/ctd/chagas/burdens

Montes G, Ponce C, Ponce E. Insecticidal Paintand Fumigant Canisters for Chagas Disease Control: Comunity acceptance in Honduras Pan American Journal of Public Health. 1999;6:311–20.

Hudock MP, Sanz-Rodriguez CE, Song Y, Chan JM, Zhang Y, Odeh S, et al. Inhibition of Trypanosoma cruzi hexokinase by bisphosphonates. J Med Chem. 2006 Jan 12;49(1):215-23.

Galvez J, Garcia-Domenech R, de Julian-Ortiz JV, Soler R. Topological Approach to Drug Design. [Erratum to document cited in CA122:177672]. Journal of Chemical Information and Computer Sciences. 1995;35(5):938.

Gozalbes R, Brun-Pascaud M, Garcia-Domenech R, Galvez J, Girard P-M, Doucet J-P, et al. Anti-Toxoplasma activities of 24 quinolones and fluoroquinolones in vitro: prediction of activity by molecular topology and virtual computational techniques. Antimicrobial Agents and Chemotherapy. 2000;44(10):2771-6.

Galvez J, de Julian-Ortiz JV, Garcia-Domenech R. Application of molecular topology to the prediction of potency and selection of novel insecticides active against malaria vectors. Theochem. 2005;727(1-3):107-13.

Mahmoudi N, de Julian-Ortiz J-V, Ciceron L, Galvez J, Mazier D, Danis M, et al. Identification of new antimalarial drugs by linear discriminant analysis and topological virtual screening. Journal of Antimicrobial Chemotherapy. 2006;57(3):489-97.

Garcia-Domenech R, Galvez J, de Julian-Ortiz JV, Pogliani L. Some New Trends in Chemical Graph Theory. Chem. Rev. 2008;108(3):1127-69.

Mahmoudi N, Garcia-Domenech R, Galvez J, Farhati K, Franetich J-F, Sauerwein R, et al. New active drugs against liver stages of Plasmodium predicted by molecular topology. Antimicrobial Agents and Chemotherapy 2008;52(4):1215-20.

Racagni GE, Machado de Domenech EE. Characterization of Trypanosoma cruzi hexokinase. Mol Biochem Parasitol. 1983 Oct;9(2):181-8.

Kier LB, Murray WJ, Randic M, Hall LH. Molecular connectivity V: connectivity series concept applied to density. J Pharm Sci. 1976 Aug;65(8):1226-30.

Kier LB, Hall LH. General definition of valence delta-values for molecular connectivity. J Pharm Sci. 1983 Oct;72(10):1170-3.

Galvez J, Garcia R, Salabert MT, Soler R. Charge Indexes. New Topological Descriptors. Journal of Chemical Information and Computer Sciences.1994;34(3):520-5.

Desmol11 software. Unidad de Investigación de Diseño de Fármacos y Conectividad Molecular. Facultad de Farmacia

Universitat de Valencia, Spain.

Dixon WJ. BMDP Statistical software. Berkeley: University of California; 1990.

Galvez J, Garcia-Domenech R, de Gregorio Alapont C, de Julian-Ortiz JV, Popa L. Pharmacological distribution diagrams: a tool for de novo drug design. Journal of Molecular Graphics. 1996;14(5):272-6.

Leon A, Liu L, Yang Y, Hudock MP, Hall P, Yin F, et al. Isoprenoid biosynthesis as a drug target: bisphosphonate inhibition of Escherichia coli K12 growth and synergistic effects of fosmidomycin. J Med Chem. 2006 Dec 14;49(25):7331-41.

Kotsikorou E, Song Y, Chan JMW, Faelens S, Tovian Z, Broderick E, et al. Bisphosphonate Inhibition of the Exopolyphosphatase Activity of the Trypanosoma brucei Soluble Vacuolar Pyrophosphatase. J. Med. Chem. 2005;48(19):6128-39.

Obojska A, Berlicki L, Kafarski P, Lejczak B, Chicca M, Forlani G. Herbicidal pyridyl derivatives of aminomethylenebisphosphonic

acid inhibit plant glutamine synthetase. Journal of Agricultural and Food Chemistry. 2004;52(11):3337-44.

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Published

2008-09-20

How to Cite

1.
GARCÍA-DOMENECH R, ESPINOZA N, GALARZA R, MORENO-PADILLA M, ROJAS-RUIZ B, ROLDAN-ARROYO L, SANCHEZ-LAVADO M, GÁLVEZ J. Application of molecular topology to the prediction of inhibition of Trypanosoma cruzi Hexokinase by bisphosphonates. Ars Pharm [Internet]. 2008 Sep. 20 [cited 2024 Aug. 24];49(3):199-20. Available from: https://revistaseug.ugr.es/index.php/ars/article/view/4948

Issue

Vol. 49 No. 3 (2008)

Section

Original Articles

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