Abstract

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.

Details

Title
Novel hybrids of 1,2,3-triazole-benzoxazole: design, synthesis, and assessment of DprE1 enzyme inhibitors using fluorometric assay and computational analysis
Author
Singh, Manisha 1 ; Batt, Sarah M 2 ; Canales, Christian S C 3 ; Pavan, Fernando R 3 ; Sethu Arun Kumar 1 ; Akshatha, Handattu S 1 ; Meduri Bhagyalalitha 1 ; Pujar, Karthik G 1 ; Bidye, Durgesh 1 ; Pujar, Gurubasavaraj V 1 ; Besra, Gurdyal S 2   VIAFID ORCID Logo 

1  Computer Aided Drug Design Lab, Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Sri Shivarathreeshwara Nagara, Mysore, India 
2  School of Biosciences, University of Birmingham, Birmingham, United Kingdom 
3  Faculty of Pharmaceutical Sciences, Paulista State University—UNESP, Araraquara, SP, Brazil 
Publication year
2024
Publication date
Dec 2024
Publisher
Taylor & Francis Ltd.
ISSN
14756366
e-ISSN
14756374
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1080/14756366.2024.2403744
ProQuest document ID
3149477208
Copyright
© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.