title: New antitrichomonal drug-like chemicals selected by bond (edge)-based TOMOCOMD-CARDD descriptors.
abstract: Bond-based quadratic indices, new TOMOCOMD-CARDD molecular descriptors, and linear discriminant analysis (LDA) were used to discover novel lead trichomonacidals. The obtained LDA-based quantitative structure-activity relationships (QSAR) models, using nonstochastic and stochastic indices, were able to classify correctly 87.91% (87.50%) and 89.01% (84.38%) of the chemicals in training (test) sets, respectively. They showed large Matthews correlation coefficients of 0.75 (0.71) and 0.78 (0.65) for the training (test) sets, correspondingly. Later, both models were applied to the virtual screening of 21 chemicals to find new lead antitrichomonal agents. Predictions agreed with experimental results to a great extent because a correct classification for both models of 95.24% (20 of 21) of the chemicals was obtained. Of the 21 compounds that were screened and synthesized, 2 molecules (chemicals G-1, UC-245) showed high to moderate cytocidal activity at the concentration of 10 microg/ml, another 2 compounds (G-0 and CRIS-148) showed high cytocidal activity only at the concentration of 100 microg/ml, and the remaining chemicals (from CRIS-105 to CRIS-153, except CRIS-148) were inactive at these assayed concentrations. Finally, the best candidate, G-1 (cytocidal activity of 100% at 10 microg/ml) was in vivo assayed in ovariectomized Wistar rats achieving promising results as a trichomonacidal drug-like compound.
authors.affiliation: Unit of Computer-Aided Molecular Biosilico Discovery and Bioinformatic Research (CAMD-BIR Unit), Faculty of Chemistry-Pharmacy, Central University of Las Villas, Villa Clara, Cuba.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Meneses-Marcel
authors.forename: Oscar M
authors.initials: OM
authors.lastname: Rivera-Borroto
authors.forename: Yovani
authors.initials: Y
authors.lastname: Marrero-Ponce
authors.forename: Alina
authors.initials: A
authors.lastname: Montero
authors.forename: Yanetsy
authors.initials: Y
authors.lastname: Machado Tugores
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Escario
authors.forename: Alicia
authors.initials: A
authors.lastname: Gómez Barrio
authors.forename: David
authors.initials: D
authors.lastname: Montero Pereira
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Nogal
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Kouznetsov
authors.forename: Cristian
authors.initials: C
authors.lastname: Ochoa Puentes
authors.forename: Arnold R
authors.initials: AR
authors.lastname: Bohórquez
authors.forename: Ricardo
authors.initials: R
authors.lastname: Grau
authors.forename: Francisco
authors.initials: F
authors.lastname: Torrens
authors.forename: Froylán
authors.initials: F
authors.lastname: Ibarra-Velarde
authors.forename: Vicente J
authors.initials: VJ
authors.lastname: Arán