Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 61, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2022.116708
Keywords
Chagas Disease; Thiosemicarbazones; Cruzipain Inhibitors; Molecular Docking
Funding
- Agencia Nacional de Promocion Cientifica y Tecnologica
- Universidad de Buenos Aires
- Consejo Nacional de Investigaciones Cientificas y Tecnologicas (Argentina)
Ask authors/readers for more resources
This study evaluated the effects of eleven thiosemicarbazones on cruzipain and investigated their interactions with the enzyme's active site and inhibition mechanism through computational methods. The results suggest that thiosemicarbazones exhibit inhibitory activity against cruzipain.
The development of cruzipain inhibitors represents one of the most attractive challenges in the search for drugs for the treatment of Chagas disease. A recombinant form of this enzyme, cruzain, has been crystallized with numerous inhibitors, excluding thiosemicarbazones. These compounds have been established as potent inhibitors of cruzain, although there is very little data in the literature of thiosemicarbazones tested on cruzipain. In this work, we present the results of the evaluation of eleven thiosemicarbazones on cruzipain, isolated from T. cruzi epimastigotes, six of them previously evaluated on cruzain. For these latter, we studied through computational methods, the mode of interaction with the active site of cruzain and the contribution of geometric parameters to the possible mechanism of action involved in the observed inhibition. Finally, from some geometric parameters analyzed on modeled TSC-cruzain complexes, a semi-quantitative relationship was established that could explain the inhibitory activity of thiosemicarbazones on cruzipain, the enzyme actually present in the parasite.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available