New antitrichomonal drug-like chemicals selected by bond (edge)-based TOMOCOMD-CARDD descriptors
| Autor: | Alfredo Meneses-Marcel, David Montero Pereira, Francisco Torrens, José Antonio Escario, Vicente J. Arán, Alina Montero, Oscar Miguel Rivera-Borroto, Ricardo Grau, Vladimir V. Kouznetsov, Yanetsy Machado Tugores, Arnold R. Romero Bohórquez, Cristian Ochoa Puentes, Alicia Barrio, Yovani Marrero-Ponce, Froylán Ibarra-Velarde, Juan José Nogal |
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| Rok vydání: | 2008 |
| Předmět: |
Drug
Adult Quantitative structure–activity relationship Stereochemistry media_common.quotation_subject Ovariectomy Drug Evaluation Preclinical Trichomonas Infections Antitrichomonal Agents Biochemistry Analytical Chemistry chemistry.chemical_compound In vivo Molecular descriptor Drug Resistance Bacterial Trichomonas vaginalis Animals Humans Rats Wistar media_common Chromatography Molecular Structure Chemistry Discriminant Analysis Linear discriminant analysis Rats Antitrichomonal agent Edge based Molecular Medicine Computer-Aided Design Female Software Biotechnology |
| Zdroj: | Journal of biomolecular screening. 13(8) |
| ISSN: | 1087-0571 |
| Popis: | 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 mg/ml, another 2 compounds (G-0 and CRIS-148) showed high cytocidal activity only at the concentration of 100 mg/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 mg/ml) was in vivo assayed in ovariectomized Wistar rats achieving promising results as a trichomonacidal drug-like compound. (Journal of Biomolecular Screening 2008:785-794). |
| Databáze: | OpenAIRE |
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