Application of molecular topology to the prediction of the antimalarial activity of 4-anilinoquinoline analogues

Authors

  • Araceli Elisa Peñarrubia Departamento de Farmacia y Tecnología Farmacéutica y Parasitología. Facultad de Farmacia. Universitat de València.
  • Raquel Peña Departamento de Farmacia y Tecnología Farmacéutica y Parasitología. Facultad de Farmacia. Universitat de València.
  • Jessica Mayorga Departamento de Farmacia y Tecnología Farmacéutica y Parasitología. Facultad de Farmacia. Universitat de València.
  • Aleksandra Urbanska Departamento de Farmacia y Tecnología Farmacéutica y Parasitología. Facultad de Farmacia. Universitat de València.
  • Jorge Gálvez Departamento de Química Física. Facultad de Farmacia. Universitat de València.
  • Ramón García-Domenech Catedrático Universitat de Valencia

DOI:

https://doi.org/10.46583/nereis_2021.13.811

Keywords:

Molecular topology, QSAR analysis, Malaria, Plasmodium falciparum

Abstract

Malaria is a parasitic disease caused by the Plasmodium protozoa and transmitted by vector of the genus Anopheles. In 2019, this disease claimed the lives of more than 400.000 people, of which 94 % are concentrated in the African region. One of the main problems with malaria control is parasite resistance to the different drugs that exist, which is why it is necessary to develop effective antimalarial alternatives. In this study, molecular topology was applied to 4-anilinoquinoline analogs with proliferation inhibitory activity of 3 Plasmodium falciparum strains, one chloroquine sensitive (D6) and two chloroquine resistant (W2 and C235); in order to develop a quantitative structure-activity (QSAR) model to predict the activity of the compounds against each of them. Using linear discriminant analysis, three functions were selected that correctly classified 87 % of the compounds analyzed in strain D6, W2 and C235, respectively. The leave some out test was carried out to validate this model. Finally, the model was applied to search for new antimalarial compounds potentially active against all three strains.

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References

World Health Organization. World Malaria Report: 20 years of global progress and challenges. Vol. WHO/HTM/GM, World Health. 2020. 238 p.

Paludismo. [consultado: 27 de enero 2021]. Disponible en: https://www.who.int/es/news-room/ fact-sheets/detail/malaria

World Health Organization. Malaria 2016-2030. 2016;35. Disponible en: http://apps.who.int/ iris/bitstream/10665/186671/1/9789243564999_spa.pdf

Gálvez J, Gálvez-Llompart M, Garci?a-Dome?nech R. Molecular topology as a novel approach for drug discovery. Expert Opinion on Drug Discovery. 2012;7(2):133-153. DOI:10.1517/1746 0441.2012.652083.

Mahmoudi N, García-Doménech 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):1215-1220.

Baptista-Peraza I, Otero-Pérez C, González-Apráez S, Pertegás-Sevilla A, Gálvez J, García- Doménech 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-Doménech 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-Doménech R, Zanni R, Gálvez-Llompart M, Gálvez J. Computational design of chemical for the control of mosquitoes and their diseases. CRC Press Taylor & Francis Group. 2018; 4:107-137.

Gálvez J, de Julián-Ortiz J, García-Doménech R. Application of molecular topology to the prediction of potency and selection of novel insecticides active against malaria vectors, J. Molec. Struct. Theochem. 2005;727:107-113 (esp. 11-13).

Mehta N, Ferrins L, Leed SE, Sciotti RJ, Pollastri MP. Optimization of Physicochemical Properties for 4-Anilinoquinoline Inhibitors of Plasmodium falciparum Proliferation. ACS Infect Dis. 2018;4(4):577-91. DOI: 10.1021/acsinfecdis.7b00212

Dassault Systèmes. BIOVIA Draw (R) Versión MDL.Draw.Editor 17.1.0.900. 2016.

Dragon para Windows (software para cálculos de descriptores moleculares) versión 5.0. Talete SRL. Milán, Italia, 2004.

Gálvez J, García-Doménech R, Salabert MT, Soler R. Charge indexes. New topological Descriptors. J Chem Inf Comput Sci. 1994;34:520-525.

Balaban AT. Highly discriminating distance-based topological index. Chemical Physics Letters 1982;89(5):399-404.

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

García-Doménech R, López-Peña W, Sanchez-Perdomo Y, Sanders JR, Sierra-Araujo MM, Zapata C, et al. Application of molecular topology to the prediction of the antimalarial activity of a group of uracil-based acyclic and deoxyuridine compounds. Int J Pharm 2008;363(1):78-84.

Statistica. StatSoft Inc. STATISTICA (Data Analysis Software System). 2007.

Gálvez J, García-Doménech R, De Gregorio Alapont C, De Julián-Ortiz JV, Popa L. Pharmacological distribution diagrams: A tool for de novo drug design. J Mol Graph 1996;14(5):272-276. DOI: 10.1016/s0263-7855(96)00081-1

Matsuno K, Ushiki J, Seishi T, Ichimura M, Giese NA, Yu J, et al. Potent and selective inhibitors of platelet-derived growth factor receptor phosphorylation. 3. Replacement of quinazoline moiety and improvement of metabolic polymorphism of 4-[4-(N-substituted (thio)carbamoyl)- 1-piperazinyl]-6,7-dimethoxyquinazoline derivatives. J Med Chem. 2003-11-06;46(23):4910- 4925.

Matsuno K, Ichimura M, Nomoto Y, Sujiwara S, Ide S, Tsukuda E, Irie J, Oda S, inventores; Kyowa Kirin Co Ltd, cesionario. Nitrogen-containing heterocyclic compounds. Canadian patent CA 2239227. 1998 Apr 9.

Kumar A, Ito A, Hirohama M, Yoshida M, Zhang KYJ. Identification of quinazolinyloxy biaryl urea as a new class of SUMO activating enzyme 1 inhibitors. Bioorg Med Chem Lett. 2013-09- 15;23(18):5145-5149.

Boschelli D, Yanong W, Boschelli F, Baerger D, Zhang N, Powell D, Ye F, Yamashita A, De- Morin F, Wu B, Tsou H, Overbeek-Klumpers E, Wissner A, inventores; Wyeth LLC, cesionario. 3-cyanoquinolines, 3-cyano-1,6-naphthyridines, and 3-cyano-1,7-naphthyridines as protein kinase inhibitors. United States Patent, US 6521618B2. 2001 Mar 28.

McCall JM, inventor; Upjohn Co, cesionario. Piperazino methyl phenyl aminoquinolines. United States Patent, US 4140775A. 1979 Feb 20

Devine W, Woodring JL, Swaminathan U, Amata E, Patel G, Erath J, et al. Protozoan Parasite Growth Inhibitors Discovered by Cross-Screening Yield Potent Scaffolds for Lead Discovery. J Med Chem. 2015-07-23;58(14):5522-5537.

Published

2021-11-15