Novel hybrids of 1,2,3-triazole-benzoxazole: design, synthesis, and assessment of DprE1 enzyme inhibitors using fluorometric assay and computational analysis
| Autor: | Manisha Singh, Sarah M. Batt, Christian S. C. Canales, Fernando R. Pavan, Sethu Arun Kumar, Handattu S. Akshatha, Meduri Bhagyalalitha, Karthik G. Pujar, Durgesh Bidye, Gurubasavaraj V. Pujar, Gurdyal S. Besra |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2024 |
| Předmět: | |
| Zdroj: | Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 39, Iss 1 (2024) |
| Druh dokumentu: | article |
| ISSN: | 14756366 1475-6374 1475-6366 |
| DOI: | 10.1080/14756366.2024.2403744 |
| Popis: | Decaprenylphosphoryl-β-D-ribose-oxidase (DprE1), a subunit of the essential decaprenylphosphoribose-2′-epimerase, plays a crucial role in the synthesis of cell wall arabinan components in mycobacteria, including the pathogen responsible for tuberculosis, Mycobacterium tuberculosis. In this study, we designed, synthesised, and evaluated 15 (BOK-1–BOK-10 and BOP-1–BOP-5) potential inhibitors of DprE1 from a series of 1,2,3-triazole ligands using a validated DprE1 inhibition assay. Two compounds, BOK-2 and BOK-3, demonstrated significant inhibition with IC50 values of 2.2 ± 0.1 and 3.0 ± 0.6 μM, respectively, whereas the standard drug (TCA-1) showed inhibition at 3.0 ± 0.2 μM. Through molecular modelling and dynamic simulations, we explored the structural relationships between selected 1,2,3-triazole compounds and DprE1, revealing key features for effective drug–target interactions. This study introduces a novel approach for designing ligands against DprE1, offering a potential therapeutic strategy for tuberculosis treatment. |
| Databáze: | Directory of Open Access Journals |
| Externí odkaz: |
|