title: A linear discrimination analysis based virtual screening of trichomonacidal lead-like compounds: outcomes of in silico studies supported by experimental results.
abstract: A 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 microg/ml and low cytotoxicity to this concentration. In particular, two heterocyclic derivatives (VA7-67 and VA7-69) maintained their efficacy at 10 microg/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 study.
authors: Department of Parasitology, Chemical Bioactive Center, Central University of Las Villas, 54830 Villa Clara, Cuba.
authors: Alfredo
authors: A
authors: Meneses-Marcel
authors: Yovani
authors: Y
authors: Marrero-Ponce
authors: Yanetsy
authors: Y
authors: Machado-Tugores
authors: Alina
authors: A
authors: Montero-Torres
authors: David Montero
authors: DM
authors: Pereira
authors: José Antonio
authors: JA
authors: Escario
authors: Juan José
authors: JJ
authors: Nogal-Ruiz
authors: Carmen
authors: C
authors: Ochoa
authors: Vicente J
authors: VJ
authors: Arán
authors: Antonio R
authors: AR
authors: Martínez-Fernández
authors: Rory N
authors: RN
authors: García Sánchez
mesh_terms: D000818:Animals; D000994:Antitrichomonal Agents / Q000737:chemistry* / Q000145:classification; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006571:Heterocyclic Compounds / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014246:Trichomonas vaginalis / Q000187:drug effects; D014584:User-Computer Interface
chemical_list: D000994:Antitrichomonal Agents; D006571:Heterocyclic Compounds