Synthesis and Biological Evaluation of New Chalcogen Semicarbazone (<i>S</i>, <i>Se</i>) and Their Azole Derivatives against Chagas Disease.

ABSTRACT: Chagas disease is caused by the eukaryote parasite Trypanosoma cruzi. Current treatment exhibits limited efficacy and selenium-based compounds emerged as promising candidates for new therapies which is surpassing its bioisoster, sulfur. We designed new thiosemicarbazones, thiazoles, selenosemicarbazones and selenazoles, using isosteric substitution. We synthesized 57 new chalcogen compounds which were evaluated against T. cruzi, C2C12 cells and cruzain, the main target of this parasite. Additionally, human cathepsin L, was tested for selectivity. Three compounds were selected, based on their activity against the intracellular amastigotes (EC₅₀ < 1 μM, SI > 10) and cruzain (IC₅₀ < 100 nM, SI > 5.55) which compared favorably with the approved drug, Benznid

SUBMITTER: Rubio-Hernandez M 

PROVIDER: S-EPMC12320831 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature