Ligand-based discovery of novel trypanosomicidal drug-like compounds: In silico identification and experimental support
dc.contributor.author | Castillo Garit, Juan Alberto | |
dc.contributor.author | Vega, Maria Celeste | |
dc.contributor.author | Rolón, Miriam | |
dc.contributor.author | Marrero Ponce, Yovani | |
dc.contributor.author | Gómez Barrio, Alicia | |
dc.contributor.author | Escario, José A. | |
dc.contributor.author | Alvarez Bello, Alfredo | |
dc.contributor.author | Montero Torres, Alina | |
dc.contributor.author | Torrens, Francisco | |
dc.contributor.author | Pérez Giménez, Facundo | |
dc.contributor.author | Arán, Vicente J. | |
dc.contributor.author | Abad, Concepción | |
dc.contributor.department | Universidad Central "Marta Abreu" de Las Villas. Centro de Bioactivos Químicos | en_US |
dc.contributor.department | Universidad de Valencia | en_US |
dc.contributor.department | Centro para el Desarrollo de la Investigación Científica. Fundación Moisés Bertoni/Díaz Gill Medicina Laboratorial. Paraguay | en_US |
dc.contributor.department | Instituto de Química Médica, CSIC. Madrid | en_US |
dc.contributor.department | Universidad Central "Marta Abreu" de Las Villas. Facultad de Química y Farmacia. Departamento de Farmacia | en_US |
dc.coverage.spatial | Santa Clara | en_US |
dc.date.accessioned | 2018-03-12T15:17:45Z | |
dc.date.available | 2018-03-12T15:17:45Z | |
dc.date.issued | 2011 | |
dc.description.abstract | Two-dimensional bond-based linear indices and linear discriminant analysis are used in this report to perform a quantitative structureeactivity relationship study to identify new trypanosomicidal compounds. A database with 143 anti-trypanosomal and 297 compounds having other clinical uses, are utilized to develop the theoretical models. The best discriminant models computed using bond-based linear indices provides accuracies greater than 90 for both training and test sets. Our models identify as anti-trypanosomals five out of nine compounds of a set of already-synthesized substances. The in vitro anti-trypanosomal activity of this set against epimastigote forms of Trypanosoma cruzi is assayed. Both models show a perfect agreement between theoretical predictions and experimental results. The compounds identified as active ones show more than 98% of anti-epimastigote elimination (AE) at a concentration of 100 mg/mL. Besides, three compounds show more than 70% of AE at a concentration of 10 mg/mL. Finally, compounds with the best “activity against epimastigote forms/unspecific cytotoxicity” ratio are evaluated using an amastigote susceptibility assay. It should be noticed that, compound Va7-71 exhibit a 100% of intracellular amastigote elimination and shows similar activity when compared to a standard trypanosomicidal as nifurtimox. Finally, we can emphasize that, the present algorithm constitutes a step forward in the search for efficient ways of discovering new anti-trypanosomal compounds | en_US |
dc.identifier.doi | 10.1016/j.ejmech.2011.04.057 | en_US |
dc.identifier.issn | 02235234 | en_US |
dc.identifier.uri | https://dspace.uclv.edu.cu/handle/123456789/8888 | |
dc.language.iso | en_US | en_US |
dc.relation.journal | European Journal of Medicinal Chemistry | en_US |
dc.rights | Este documento es propiedad patrimonial de la editorial ELSEVIER BV que se reserva todos los derechos. La UCLV reproduce el mismo con fines exclusivamente educativos y cientificos, restringiendo su empleo a la comunidad universitaria de nuestro centro. Los usarios están obligados a emplear este documento sin ánimos de lucro y sin realizar otras reproducciones, así como a citar el material y sus autores cada vez que sea utilizado. | en_US |
dc.rights.holder | Elsevier BV | en_US |
dc.subject | Bond-based linear indices | en_US |
dc.subject | Trypanosoma cruzi | en_US |
dc.subject | Trypanosomicidal | en_US |
dc.subject | Anti-epimastigote elimination | en_US |
dc.subject | Amastigote susceptibility assay | en_US |
dc.subject.other | Trypanosoma cruzi | en_US |
dc.title | Ligand-based discovery of novel trypanosomicidal drug-like compounds: In silico identification and experimental support | en_US |
dc.type | Article | en_US |
dc.type.article | 1 | en_US |
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