1. Thio- and selenosemicarbazones as antiprotozoal agents against Trypanosoma cruzi and Trichomonas vaginalis .
- Author
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Ibáñez-Escribano A, Fonseca-Berzal C, Martínez-Montiel M, Álvarez-Márquez M, Gómez-Núñez M, Lacueva-Arnedo M, Espinosa-Buitrago T, Martín-Pérez T, Escario JA, Merino-Montiel P, Montiel-Smith S, Gómez-Barrio A, López Ó, and Fernández-Bolaños JG
- Subjects
- Antiprotozoal Agents chemical synthesis, Antiprotozoal Agents chemistry, Dose-Response Relationship, Drug, Molecular Structure, Parasitic Sensitivity Tests, Semicarbazones chemical synthesis, Semicarbazones chemistry, Structure-Activity Relationship, Antiprotozoal Agents pharmacology, Semicarbazones pharmacology, Trichomonas vaginalis drug effects, Trypanosoma cruzi drug effects
- Abstract
Herein, we report the preparation of a panel of Schiff bases analogues as antiprotozoal agents by modification of the stereoelectronic effects of the substituents on N-1 and N-4 and the nature of the chalcogen atom (S, Se). These compounds were evaluated towards Trypanosoma cruzi and Trichomonas vaginalis . Thiosemicarbazide 31 showed the best trypanocidal profile (epimastigotes), similar to benznidazole (BZ): IC
50 ( 31 )=28.72 μM (CL-B5 strain) and 33.65 μM (Y strain), IC50 (BZ)=25.31 μM (CL-B5) and 22.73 μM (Y); it lacked toxicity over mammalian cells (CC50 > 256 µM). Thiosemicarbazones 49 , 51 and 63 showed remarkable trichomonacidal effects (IC50 =16.39, 14.84 and 14.89 µM) and no unspecific cytotoxicity towards Vero cells (CC50 ≥ 275 µM). Selenoisosters 74 and 75 presented a slightly enhanced activity (IC50 =11.10 and 11.02 µM, respectively). Hydrogenosome membrane potential and structural changes were analysed to get more insight into the trichomonacidal mechanism.- Published
- 2022
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