期刊
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
卷 37, 期 1, 页码 781-791出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/14756366.2022.2041629
关键词
Trypanosoma cruzi; Trichomonas vaginalis; antiprotozoal agents; thio(seleno)semicarbazones; unspecific cytotoxicity; MoA
资金
- Junta de Andalucia [FQM-134]
- UCM Research Group [911120]
- Mexican CONACYT [CB-2015/257465]
- [PID2020116460RB-I00]
- [MCIN/AEI/10.13039/501100011033]
In this study, a series of antiprotozoal compounds were synthesized by modifying the substituents on N-1 and N-4 and the nature of the chalcogen atom. The compounds showed good activity against Trypanosoma cruzi and Trichomonas vaginalis. Thiosemicarbazide 31 exhibited the best trypanocidal activity, while thiosemicarbazones 49, 51, and 63 showed remarkable trichomonacidal effects. The compounds were also found to be non-toxic to mammalian cells.
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): IC50 (31)=28.72 mu M (CL-B5 strain) and 33.65 mu M (Y strain), IC50 (BZ)=25.31 mu M (CL-B5) and 22.73 mu M (Y); it lacked toxicity over mammalian cells (CC50 > 256 mu M). Thiosemicarbazones 49, 51 and 63 showed remarkable trichomonacidal effects (IC50 =16.39, 14.84 and 14.89 mu M) and no unspecific cytotoxicity towards Vero cells (CC50 >= 275 mu M). Selenoisosters 74 and 75 presented a slightly enhanced activity (IC50=11.10 and 11.02 mu M, respectively). Hydrogenosome membrane potential and structural changes were analysed to get more insight into the trichomonacidal mechanism.
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