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Drug repositioning for novel antitrichomonas from known antiprotozoan drugs using hierarchical screening

  • Alfredo Meneses-Marcel
  • , Yovani Marrero-Ponce*
  • , Alexandra Ibáñez-Escribano
  • , Alicia Gómez-Barrio
  • , José A. Escario
  • , Stephen J. Barigye
  • , Enrique Terán
  • , Cesar R. García-Jacas
  • , Yanetsy MacHado-Tugores
  • , Juan J. Nogal-Ruiz
  • , Vicente J. Arán-Redó
  • *Corresponding author for this work
  • Universidad Central Marta Abreu de Las Villas
  • UCM
  • Computer-Aided Molecular Biosilico Discovery and Bioinformatics Research International Network (CAMD-BIR IN)
  • Fundación Universitaria Tecnológico Comfenalco
  • McGill University
  • Universidad San Francisco de Quito
  • Universidad Nacional Autónoma de México
  • Pontificia Universidad Católica del Ecuador
  • CSIC - Medicinal Chemistry Institute

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Aim: Metronidazole is the most widely used drug in trichomoniasis therapy. However, the emergence of metronidazole-resistant Trichomonas vaginalis isolates calls for the search for new drugs to counter the pathogenicity of these parasites. Results: Classification models for predicting the antitrichomonas activity of molecules were built. These models were employed to screen antiprotozoal drugs, from which 20 were classified as active. The in vitro experiments showed moderate to high activity for 19 of the molecules at 10 μg/ml, while 3 compounds yielded higher activity than the reference at 1 μg/ml. The 11 most active chemicals were evaluated in vivo using Naval Medical Research Institute (NMRI) mice. Conclusion: Benznidazole showed similar results as metronidazole, and can thus be considered as a potential candidate in antitrichomonas therapy.

Original languageEnglish
Pages (from-to)863-878
Number of pages16
JournalFuture Medicinal Chemistry
Volume10
Issue number8
DOIs
StatePublished - Apr 2018

Keywords

  • QSAR
  • QuBiLS-MAS
  • ToMoCoMD-CARDD
  • Trichomonas vaginalis
  • antitrichomonas

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