Evaluating the Antitrypanosomatid Activity of Thiazolyl–Isatins: Synthesis, Biological Evaluation, and Electronic Structure Analysis Using the Semiempirical GFN2‐xTB Method
Randomized trial evaluates anti-trypanosomatid activity in synthesized compounds, suggesting new treatment options.
Key Points
The aim is to evaluate new hybrid molecules for their ability to combat Trypanosomatidae, addressing the need for novel therapies.
Synthesis of 43 new hybrid molecules combining isatin and thiazole scaffolds.
In vitro evaluation of anti-Trypanosomatidae activity against Trypanosoma cruzi and Leishmania species.
In silico analyses for bioavailability and electronic structure using the GFN2-xTB method.
12 compounds showed anti-tryPanoma cruzi activity with EC50 values from 1.30 to 3.14 µM, similar to benznidazole (EC50 = 3.17 µM).
36 compounds had EC50 values lower than miltefosine (EC50 = 26.74 µM) in assays against Leishmania amazonensis promastigotes, with the most potent at 1.40 µM.
All compounds showed favorable bioavailability scores and a moderate correlation with trypanothione reductase activity (ρ = 0.50, p < 0.05).