A sequential procedure for rapid and accurate identification of putative trichomonacidal agents

Journal of Microbiological Methods
Alexandra Ibáñez-EscribanoJosé Antonio Escario

Abstract

In the current report, a sequential step-wise methodology based on in silico, in vitro and in vivo experimental procedures for the prompt detection of potential trichomonacidal drugs is proposed. A combinatorial of 12 QSAR (Quantitative Structure-Activity Relationship) models based on Linear Discrimination Analysis (LDA) are suggested for the rational identification of new trichomonacidal drugs from virtual screening of in house chemical libraries and drug databases. Subsequently, compounds selected as potential anti-trichomonas are screened in vitro against Trichomonas vaginalis. Finally, molecules with specific trichomonacidal activity are evaluated in vivo. Herein, different molecules were exposed to the proposed methodology. Firstly, the agents were virtually screened and two of the eight molecules (G-1 and dimetridazole) were classified as trichomonacidals by the 12 models. Subsequently both drugs were proved in vitro and in vivo following the workflow procedure. Although a remarkable in vitro activity was observed in both cases, dimetridazole achieved higher MIC100 activity than metronidazole against the resistant isolate. Furthermore, the in vivo models showed a remarkable reduction of lesions of more than 55% in both co...Continue Reading

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Citations

Mar 28, 2016·European Journal of Medicinal Chemistry·Cristina Fonseca-BerzalVicente J Arán
Mar 29, 2018·Future Medicinal Chemistry·Alfredo Meneses-MarcelVicente J Arán-Redó
Feb 9, 2021·Bioorganic & Medicinal Chemistry Letters·Alexandra Ibáñez-EscribanoAlicia Gómez-Barrio

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