| Autor: |
Manu, Prince, Mensah, Jehoshaphat Oppong, Gasu, Edward Ntim, Borquaye, Lawrence Sheringham |
| Zdroj: |
Journal of Biomolecular Structure and Dynamics; November 2024, Vol. 42 Issue: 17 p8920-8936, 17p |
| Abstrakt: |
AbstractTrypanosoma cruziis the parasite that causes the chronic malady known as Chagas disease (CD). Only nifurtimox and benznidazole are currently approved to treat CD in acute and chronic phases. To minimize the danger of disease transmission and as a therapy, new compounds that are safer and more effective are required. It has been demonstrated that Amaryllidaceaeplants suppress the growth of T. cruzi –the causative agent of CD. However, little research has been done on their potential protein targets in the parasite. In this study, an in-silicoapproach was used to investigate the interactions of the Amaryllidaceaealkaloids with trans-sialidase, a confirmed protein target of T. cruzi. The nature and efficiency of the main binding modes of the alkaloids were investigated by molecular docking. Trans-sialidase active site residues were bound by the alkaloids with binding energies varying from −8.9 to −6.9 kcal/mol. From the molecular docking investigation, all the alkaloids had strong interactions with the crucial amino acid residues (Glu230, Tyr342, and Asp59) required for trans-sialidase catalysis. Montanine was the most stable compound throughout the molecular dynamics simulation and had a favorable docking binding energy (−8.9 kcal/mol). The binding free energy (MM-GBSA) of the montanine complex was −14.6 kcal/mol. The pharmacokinetic properties investigated demonstrated that all the evaluated compounds exhibit suitable oral administration requirements. Overall, this in silicostudy suggests that the Amaryllidaceae alkaloids could potentially act as inhibitors of trans-sialidase.Communicated by Ramaswamy H. Sarma |
| Databáze: |
Supplemental Index |
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