Thio- and selenosemicarbazones as antiprotozoal agents against Trypanosoma cruzi and Trichomonas vaginalis

J Enzyme Inhib Med Chem. 2022 Dec;37(1):781-791. doi: 10.1080/14756366.2022.2041629.

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): IC50 (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.

Keywords: MoA; Trichomonas vaginalis; Trypanosoma cruzi; antiprotozoal agents; thio(seleno)semicarbazones; unspecific cytotoxicity.

MeSH terms

  • Antiprotozoal Agents / chemical synthesis
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Semicarbazones / chemical synthesis
  • Semicarbazones / chemistry
  • Semicarbazones / pharmacology*
  • Structure-Activity Relationship
  • Trichomonas vaginalis / drug effects*
  • Trypanosoma cruzi / drug effects*

Substances

  • Antiprotozoal Agents
  • Semicarbazones

Grants and funding

The present work was financially supported by Grant PID2020-116460RB-I00, funded by MCIN/AEI/10.13039/501100011033, Junta de Andalucía (FQM-134), UCM Research Group ref. 911120 Epidemiología, Diagnóstico y Terapia antiparasitaria (PARADET) and the Mexican CONACYT (CB-2015/257465).