Ligand-based discovery of novel trypanosomicidal drug-like compounds: In silico identification and experimental support

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dc.contributor.authorCastillo Garit, Juan Alberto
dc.contributor.authorVega, Maria Celeste
dc.contributor.authorRolón, Miriam
dc.contributor.authorMarrero Ponce, Yovani
dc.contributor.authorGómez Barrio, Alicia
dc.contributor.authorEscario, José A.
dc.contributor.authorAlvarez Bello, Alfredo
dc.contributor.authorMontero Torres, Alina
dc.contributor.authorTorrens, Francisco
dc.contributor.authorPérez Giménez, Facundo
dc.contributor.authorArán, Vicente J.
dc.contributor.authorAbad, Concepción
dc.contributor.departmentUniversidad Central "Marta Abreu" de Las Villas. Centro de Bioactivos Químicosen_US
dc.contributor.departmentUniversidad de Valenciaen_US
dc.contributor.departmentCentro para el Desarrollo de la Investigación Científica. Fundación Moisés Bertoni/Díaz Gill Medicina Laboratorial. Paraguayen_US
dc.contributor.departmentInstituto de Química Médica, CSIC. Madriden_US
dc.contributor.departmentUniversidad Central "Marta Abreu" de Las Villas. Facultad de Química y Farmacia. Departamento de Farmaciaen_US
dc.coverage.spatialSanta Claraen_US
dc.date.accessioned2018-03-12T15:17:45Z
dc.date.available2018-03-12T15:17:45Z
dc.date.issued2011
dc.description.abstractTwo-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 compoundsen_US
dc.identifier.doi10.1016/j.ejmech.2011.04.057en_US
dc.identifier.issn02235234en_US
dc.identifier.urihttps://dspace.uclv.edu.cu/handle/123456789/8888
dc.language.isoen_USen_US
dc.relation.journalEuropean Journal of Medicinal Chemistryen_US
dc.rightsEste 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.holderElsevier BVen_US
dc.subjectBond-based linear indicesen_US
dc.subjectTrypanosoma cruzien_US
dc.subjectTrypanosomicidalen_US
dc.subjectAnti-epimastigote eliminationen_US
dc.subjectAmastigote susceptibility assayen_US
dc.subject.otherTrypanosoma cruzien_US
dc.titleLigand-based discovery of novel trypanosomicidal drug-like compounds: In silico identification and experimental supporten_US
dc.typeArticleen_US
dc.type.article1en_US

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