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

作者：Meneses Marcel Alfredo; Marrero Ponce Yovani; Ibanez Escribano Alexandra; Gomez Barrio Alicia; Escario Jose A; Barigye Stephen J; Teran Enrique; Garcia Jacas Cesar R; Machado Tugores Yanetsy; Nogal Ruiz Juan J; Aran Redo Vicente J

来源：Future Medicinal Chemistry, 2018, 10(8): 863-878.

DOI：10.4155/fmc-2016-0211

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

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 mu g/ml, while 3 compounds yielded higher activity than the reference at 1 mu g/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.

• 出版日期2018-4