Application of molecular topology to the prediction of antiparasitic activity against Giardia intestinalis and Trichomonas vaginalis of 2-Acylamino-nitro-1,3-thiazole products

Authors

  • C. Izquierdo-García Departamento de Farmacia y Tecnología Farmacéutica y Parasitología. Facultad de Farmacia. Universitat de València.
  • E. Lindsay-Pérez Departamento de Farmacia y Tecnología Farmacéutica y Parasitología. Facultad de Farmacia. Universitat de València.
  • R. Alaoui-Bouhamid Departamento de Farmacia y Tecnología Farmacéutica y Parasitología. Facultad de Farmacia. Universitat de València.
  • M. Parra-Civera Departamento de Farmacia y Tecnología Farmacéutica y Parasitología. Facultad de Farmacia. Universitat de València.
  • J. Gálvez Departamento de Química Física. Facultad de Farmacia. Universitat de València.
  • R. García-Domenech Departamento de Química Física. Facultad de Farmacia. Universitat de València.

DOI:

https://doi.org/10.46583/nereis_2020.12.586

Keywords:

molecular topology, QSAR, Giardia intestinalis, Trichomonas vaginalis

Abstract

Giardia intestinalis and Trichomonas vaginalis stand out for their clinical importance. G. intestinalis causes giardiasis, a parasitism of great epidemiological and clinical importance due to its high prevalence. T. vaginalis causes trichomoniasis, the non-viral sexually transmitted disease (STD) with the highest incidence in the world. Both parasitisms share the same pharmacological treatment: nitroimidazoles. Molecular topology has been applied in searching for derivatives of 2-Acylamino-nitro-1,3-thiazole with antiparasitic activity against G. intestinalis and T. vaginalis. After using linear discriminant analyses, results show a model that could correctly classify the activity of 92.85 % of the compounds studied in both parasites. To predict antiparasitic activity, a multilinear regression analysis was carried out that could explain 83.2 % of the variance in G. intestinalis, and 89.4 % in T. vaginalis. Finally, a molecular screening was carried out to look for new potentially active compounds against both parasites.

References

Centers for Disease Control and Prevention. Giardiasis. U.S. Department of Health & Human Services. 2017. [Consultado: 16 de febrero de 2020]. Disponible en: https://www.cdc.gov/parasites/giardia/index.html

Hugo DL. Giardia y giardiasis. Instituto de Investigaciones Médicas Mercedes y Martín Ferreyra. 2006;66:70-4.

Michael JG. Giardiasis. Parasitic diseases of the liver and intestines. 1996;25:493-515.

Alexandra IE, Alicia GB. Trichomonas vaginalis: la versatilidad de un parásito tenaz. Real Acad Nac Farm. 2017;83(1):10-47.

Heine P, McGregor JA. Trichomonas vaginalis: a reemerging pathogen. Clin Obstet Gynecol. 1993;36:137-44.

Centers for Disease Control and Prevention. Trichomoniasis. U.S. Department of Health & Human Services. 2017. [Consultado: 16 de febrero de 2020]. Disponible en: https://www.cdc.gov/std/trichomonas/default.htm

Nava-Zuazo C, Chávez-Silva F, Moo-Puc R, Chan-Bacab MJ, Ortega-Morales BO, Moreno-Díaz H et al. 2-acylamino-5-nitro-1, 3-thiazoles: preparation and in vitro bioevaluation against four neglected protozoan parasites. Bioor Med Chem. 2014;22(5):1626-33.

Gálvez J, Gálvez-Llompart R, García-Domenech R. Molecular topology as a novel approach for drug discovery. Expert Opin Drug Discov. 2012;7(2):133-53.

Zanni R, Galvez-Llompart M, García-Domenech R, J. Gálvez. Latest advances in molecular topology applications for drug discovery. Expert Opin Drug Discov. 2015;10(9):945-57.

Rodríguez MÁM, López-Peñalver RJS, Tomás GA, Álvarez JG, Gálvez-Llompart M, García-Domenech R. Aplicación de la topología molecular a la predicción y optimización de la actividad repelente de mosquitos de derivados de la N-acylpiperidina. Nereis. Interdisciplinary IberoAmerican Journal of Methods, Modelling and Simulation. 2014;6:19-26.

Mahmoudi N, García-Domenech R, Gálvez J, Farhati K, Franetich JF, Sauerwein R et al. New active drugs against liver stages of Plasmodium predicted by molecular topology. Antimicrob Agents Chemother 2008 Apr. 52(4):1215-20.

Baptista-Peraza I, Otero-Pérez C, González-Apráez S, Pertegás-Sevilla A, Galvez J, Garcia-Domenech R. Aplicación de la Topología Molecular al Análisis de la Actividad Antimalárica de 4-Aminobiciclo [2.2. 2] Octan-2-il 4-Aminobutanoatos y sus Análogos Etanoatos y Propanoatos. Nereis. Interdisciplinary Ibero-American Journal of Methods, Modelling and Simullation. 2019;11:51-64.

Carrillo JS, Rizza C, Álvarez BE, Hernández D, Gálvez J, García-Domenech R. Aplicación de la Topología Molecular en la búsqueda de nuevos compuestos basados en Azaauronas derivados de las Auronas naturales como potenciales antimaláricos. Nereis. Interdisciplinary Ibero-American Journal of Methods, Modelling and Simulation. 2017;9:49-62.

García-Domenech R, Zanni R, Galvez-Llompart M, Galvez J, Computational design of chemical for the control of mosquitoes and their diseases (2018) CRC Press Taylor & Francis Group, Chapter 4, 107-37.

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

Perkin Elmer Informatics I. ChemDraw® Professional version 16.0.

Dragon for Windows (Software for Molecular Descriptor Calculations) versión 5.0. Talete SRL. Milan, Italy, 2004.

StatSoft, Inc. Statistica (Data Analysis Software System) versión 8. StatSoft. Tulsa, Ok, USA, 2008.

Gálvez J, García-Domenech R, De Gregorio Alapont C, De Julián-Ortiz J, Popa L. Pharmacological distribution diagrams: a tool for de novo drug design. J Mol Graph. 1996;14(5):272-6.

Todeschini R, Consonni V, Mauri, Pavan M. Dragon for windows (software for molecular descriptor calculations), version 5.4. Talete SRL. Milan, Italy 2006.

Galvez J, García-Domenech R, Salabert M, Soler R. Charge indexes. New topological descriptors. J. Chem. Inf. Comput. Sci. 1994;34:520-5.

Published

2020-07-16