Aplicación de topología molecular a la predicción de la actividad frente a Trypanosoma cruzi de compuestos derivados nitrotriazoles

  1. Cristina Rodríguez Grande 1
  2. Beatriz Villalba de Gregorio 1
  3. María Amelia Bort Carbonell 1
  4. Claudio Norberto Giordanelly Mendicoa 1
  5. Jorge Gálvez Álvarez 1
  6. Ramón García-Domenech 1
  1. 1 Facultad de Farmacia. Universitat de València.
Zeitschrift:
Nereis: revista iberoamericana interdisciplinar de métodos, modelización y simulación

ISSN: 1888-8550

Datum der Publikation: 2016

Nummer: 8

Seiten: 11-22

Art: Artikel

DIALNET GOOGLE SCHOLAR lock_openDialnet editor

Andere Publikationen in: Nereis: revista iberoamericana interdisciplinar de métodos, modelización y simulación

Zusammenfassung

The Chagas disease, caused by the protozoo Trypanosoma cruzi, is considered the most important unattended tropical disease. The drugs destined to treat this disease present several problems, which implies the need to look for new drugs. In the present work 22 nitrotriazole derivatives that have proven to be effective as antitrypanosoma in in vivo tests, are studied. Using discriminant analysis, it was obtained a correct classification as active compounds of 100% of them. Furthermore to predict the antiparasitic activity, a multilinear regression analysis was carried out and it yielded a predictive of 85% of the variance. The validation of this model was done by leave-one-out cross-validation. Finally, the model was applied to search for new potential new active compounds against T. cruzi.

Bibliographische Referenzen

  • WHO sede WEB, Neglected tropical diseases [actualizado 6 de diciembre de 2010; acceso 10 de diciembre de 2015]. Disponible en: http://www.who.int/topics/tropical_diseases/qa/faq/es/.
  • K. Stuart, R. Brun, S. Croft, A. Fairlamb, R. E. Gürtler, J. McKerrow, S. Reed, R. Tarleton. Kinetoplastids: related protozoan pathogens, different diseases. Journal of Clinical Investigation 118 (2008) 1301-1310.
  • G. A. Schmunis, Z. E. Yadon. Chagas disease: a Latin American health problem becoming a world health problem. Acta tropica 115 (2010) 14-21.
  • C. Young, P. Losikoff, A. Chawla, L. Glasser, E. Forman. Transfusion-acquired Trypanosoma cruzi infection. Transfusion 47 (2007) 540-544.
  • Anonymous. Chagas disease after organ transplantation [actualizado 28 de julio de 2006; acceso 12 de diciembre de 2015]. CDC, Morbidity and Mortality Weekly Report (MMWR) 55 (2006) 798-800. Disponible en: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5529a3.htm.
  • R. E. Gurtler, E. L. Segura, J. E. Cohen. Congenital transmission of Trypanosoma cruzi infection in Argentina. Emerging Infectious Diseases Journal 9 (2003) 29-32.
  • P. R. Benchimol Barbosa. The oral transmission of Chagas’ disease: an acute form of infection responsible for regional outbreaks. International Journal of Cardiology 112 (2006) 132-133.
  • J. C. Dias, Cecilio Romaña. Romaña’s sign and Chagas’ disease. Revista da Sociedade Brasileira de Medicina Tropical 30 (1997) 407-413.
  • WHO sede WEB, Chagas disease (American trypanosomiasis) [actualizado marzo de 2015; acceso 11 de diciembre de 2015]. Disponible en: http://www.who.int/mediacentre/factsheets/fs340/en/.
  • M. V. Papadopoulou, W. D. Bloomer, H. S. Rosenzweig, S. R. Wilkinson, M. Kaiser. Novel nitro (triazole/imidazole)-based heteroarylamides/sulfonamides as potential antitrypanosomal agents. European Journal of Medicinal Chemistry 87 (2014) 79-88.
  • G. I. Lepesheva, F. Villalta, M. R. Waterman. Targeting Trypanosoma cruzi sterol 14α-demethylase (CYP51). Advances in parasitology 75 (2011) 65-87.
  • F. Villalta, M. C. Dobish, P. N. Nde, Y. Y. Kleshchenko, T. Y. Hargrove, C. A. Johnson, M. R. Waterman, J. N. Johnston, G. I. Lepesheva. VNI cures acute and chronic experimental Chagas disease. Journal of Infectious Diseases 208 (2013) 504- 511.
  • J. Clayton. Chagas disease: pushing through the pipeline. Nature 465 (2010) S12-S15.
  • R. Bretón Martínez, C. Torrico Ovando, N. Torrico Ovando, M. Gálvez-Llompart, J. Gálvez, R. García-Domenech. Aplicación de topología molecular a la predicción de la actividad frente a Trypanosoma brucei rhodesiense de compuestos bicíclicos derivados del 4-metilpiperazina. Nereis 7 (2014) 27-37.
  • N. Mahmoudi, R. García Doménech, J. Gálvez, K. Farhati, J. F. Franetich, R. Sauerwein et al. New active drugs against liver stages of Plasmodium predicted by molecular topology. Antimicrob Agents Chemother 52 (2008) 1215-1220.
  • J. Gálvez, M. Gálvez-Llompart, R. García-Doménech. Molecular topology as a novel approach for drug discovery. Expert Opin Drug Discov 7 (2012) 133-153.
  • R. Zanni, M. Galvez-Llompart, C. Morell, N. Rodríguez-Henche, I. Díaz-Laviada, M. Recio-Iglesias, R. GarciaDomenech, J. Galvez. Novel Cancer Chemotherapy Hits by Molecular Topology: Dual Akt and Beta-Catenin Inhibitors. PLOS ONE (2015), DOI:10.1371/journal.pone.0124244.
  • L. B. Kier, L. H. Hall. Molecular Connectivity in Chemistry and Drug Research. Academic Press, London, 1976.
  • L. B. Kier, L. H. Hall. Molecular Connectivity in Structure-Activity Analysis. Wiley, New York, 1986.
  • J. Galvez, R. Garcia-Domenech, M. T. Salabert, R. Soler. Charge indexes. New topological Descriptors. J Chem Inf Comput Sci 34 (1994) 520-525.
  • H. J. Wiener. Structural determination of paraffin boiling points. Journal of the American Chemical Society 69 (1) (1947) 17-20.
  • DESMOL11 Software. Unidad de Investigación de Diseño de Fármacos y Conectividad Molecular. Facultad de Farmacia, Universitat de València, Spain.
  • Statistica 8.0 (2008). Statsoft Inc http://www.statsoft.com.
Fuente de los datos: Dialnet