A linear discrimination analysis based virtual screening of trichomonacidal lead-like compounds: outcomes of in silico studies supported by experimental results

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dc.contributor.authorMeneses Marcel, Alfredo
dc.contributor.authorMarrero Ponce, Yovani
dc.contributor.authorMachado Tugores, Yanetsy
dc.contributor.authorMontero Torres, Alina
dc.contributor.authorMontero Pereira, David
dc.contributor.authorEscario, José Antonio
dc.contributor.authorNogal Ruiz, Juan José
dc.contributor.authorOchoa, Carmen
dc.contributor.authorArán, Vicente J.
dc.contributor.authorMartínez Fernández, Antonio R.
dc.contributor.authorGarcía Sánchez, Rory N.
dc.contributor.departmentUniversidad Central "Marta Abreu" de Las Villas. Centro de Bioactivos Químicosen_US
dc.contributor.departmentUniversidad Central "Marta Abreu" de Las Villas. Facultad de Química y Farmacia. Departamento de Farmaciaen_US
dc.contributor.departmentInstituto de Química Médica, CSIC. Madriden_US
dc.contributor.departmentUniversidad Nacional de la Amazonía Peruana. Laboratorio de Investigación de Productos Naturales Antiparasitarios de la Amazoníaen_US
dc.coverage.spatialSanta Claraen_US
dc.date.accessioned2018-03-09T00:27:51Z
dc.date.available2018-03-09T00:27:51Z
dc.date.issued2005
dc.description.abstractA computational (virtual) screening test to identify potential trichomonacidals has been developed. Molecular structures of trichomonacidal and non-trichomonacidal drugs were represented using stochastic and non-stochastic atom-based quadratic indices and a linear discrimination analysis (LDA) was trained to classify molecules regarding their antiprotozoan activity. Validation tests revealed that our LDA-QSAR models recognize at least 88.24% of trichomonacidal lead-like compounds and suggest using this methodology in virtual screening protocols. These classification functions were then applied to find new lead antitrichomonal compounds. In this connection, the biological assays of eight compounds, selected by computational screening using the present models, give good results (87.50% of good classification). In general, most of the compounds showed high activity against Trichomonas vaginalis at the concentration of 100 lg/ml and low cytotoxicity to this concentration. In particular, two heterocyclic derivatives (VA7-67 and VA7-69) maintained their efficacy at 10 lg/ml with an important trichomonacidal activity (100.00% of reduction),but it is remarkable that the compound VA7-67 did not show cytotoxic effects in macrophage cultivations. This result opens a door to a virtual study considering a higher variability of the structural core already evaluated, as well as of other chemicals not included in this studyen_US
dc.identifier.doi10.1016/j.bmcl.2005.05.124en_US
dc.identifier.issn0960-894Xen_US
dc.identifier.urihttps://dspace.uclv.edu.cu/handle/123456789/8865
dc.language.isoen_USen_US
dc.relation.journalBioorganic & Medicinal Chemistry Lettersen_US
dc.rightsEste documento es propiedad patrimonial de la editorial Elsevier Ltd. 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 amimos de lucro y sin realizar otras reproducciones, asi como a citar el material y sus autores cada vez que sea utilizadoen_US
dc.rights.holderElsevier Ltd.en_US
dc.subjectAtom-based quadratic indicesen_US
dc.subjectíndices cuadráticosen_US
dc.subjectLDA-based modelen_US
dc.subjectTrichomonacidal activityen_US
dc.subjectCytotoxic propertiesen_US
dc.subjectTrichomomasen_US
dc.subjectDiseño de fármacosen_US
dc.titleA linear discrimination analysis based virtual screening of trichomonacidal lead-like compounds: outcomes of in silico studies supported by experimental resultsen_US
dc.typeArticleen_US
dc.type.article1en_US

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