Next Article in Journal
Coriolic Acid (13-(S)-Hydroxy-9Z, 11E-octadecadienoic Acid) from Glasswort (Salicornia herbacea L.) Suppresses Breast Cancer Stem Cell through the Regulation of c-Myc
Previous Article in Journal
Production of Defense Phenolics in Tomato Leaves of Different Age
Previous Article in Special Issue
Modified Nucleic Acids: Expanding the Capabilities of Functional Oligonucleotides
Open AccessArticle

Design and Synthesis of Various 5′-Deoxy-5′-(4-Substituted-1,2,3-Triazol-1-yl)-Uridine Analogues as Inhibitors of Mycobacterium tuberculosis Mur Ligases

1
Institute of Organic and Analytical Chemistry, CNRS UMR 7311, Universite d’Orléans, Rue de Chartres, CEDEX 2, 45067 Orleans, France
2
Department of Biomedical Science, Acharya Narendra Dev College, University of Delhi, New Delhi 110019, India
3
G N Ramachandran Knowledge of Centre, Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology (CSIR-IGIB), Room No. 130, Mathura Road, New Delhi 110025, India
*
Authors to whom correspondence should be addressed.
Academic Editor: Jussara Amato
Molecules 2020, 25(21), 4953; https://doi.org/10.3390/molecules25214953
Received: 14 September 2020 / Revised: 17 October 2020 / Accepted: 19 October 2020 / Published: 26 October 2020
(This article belongs to the Special Issue Nucleosides – Nucleotides – Oligonucleotides)
The synthesis of hitherto unknown 5′-deoxy-5′-(4-substituted-1,2,3-triazol-1-yl)-uridine and its evaluation, through an one-pot screening assay, against MurA-F enzymes involved in Mycobacterium tuberculosis (Mtb), are described. Starting from UDP-N-acetylmuramic acid (UDP-MurNAc), the natural substrate involved in the peptidoglycan biosynthesis, our strategy was to substitute the diphosphate group of UDP-MurNAc by a 1,2,3-triazolo spacer under copper-catalyzed azide-alkyne cycloaddition conditions. The structure-activity relationship was discussed and among the 23 novel compounds developed, N-acetylglucosamine analogues 11c and 11e emerged as the best inhibitors against the Mtb MurA-F enzymes reconstruction pathway with an inhibitory effect of 56% and 50%, respectively, at 100 μM. Both compounds are selective inhibitors of Mtb MurE, the molecular docking and molecular dynamic simulation suggesting that 11c and 11e are occupying the active site of Mtb MurE ligase. View Full-Text
Keywords: Mur ligase; nucleoside analogues; copper-catalyzed azide-alkyne cycloaddition; antibacterial agents; molecular modelling Mur ligase; nucleoside analogues; copper-catalyzed azide-alkyne cycloaddition; antibacterial agents; molecular modelling
Show Figures

Figure 1

MDPI and ACS Style

Hervin, V.; Arora, R.; Rani, J.; Ramchandran, S.; Bajpai, U.; Agrofoglio, L.A.; Roy, V. Design and Synthesis of Various 5′-Deoxy-5′-(4-Substituted-1,2,3-Triazol-1-yl)-Uridine Analogues as Inhibitors of Mycobacterium tuberculosis Mur Ligases. Molecules 2020, 25, 4953.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop