{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:54:33Z","timestamp":1789001673762,"version":"build-2803163510"},"reference-count":24,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T00:00:00Z","timestamp":1603670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-11-LABX-0029"],"award-info":[{"award-number":["ANR-11-LABX-0029"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The synthesis of hitherto unknown 5\u2032-deoxy-5\u2032-(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 \u03bcM. 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.<\/jats:p>","DOI":"10.3390\/molecules25214953","type":"journal-article","created":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T10:38:35Z","timestamp":1603708715000},"page":"4953","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Design and Synthesis of Various 5\u2032-Deoxy-5\u2032-(4-Substituted-1,2,3-Triazol-1-yl)-Uridine Analogues as Inhibitors of Mycobacterium tuberculosis Mur Ligases"],"prefix":"10.3390","volume":"25","author":[{"given":"Vincent","family":"Hervin","sequence":"first","affiliation":[{"name":"Institute of Organic and Analytical Chemistry, CNRS UMR 7311, Universite d\u2019Orl\u00e9ans, Rue de Chartres, CEDEX 2, 45067 Orleans, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritu","family":"Arora","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Acharya Narendra Dev College, University of Delhi, New Delhi 110019, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyoti","family":"Rani","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Acharya Narendra Dev College, University of Delhi, New Delhi 110019, India"},{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivasan","family":"Ramchandran","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urmi","family":"Bajpai","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Acharya Narendra Dev College, University of Delhi, New Delhi 110019, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6083-0810","authenticated-orcid":false,"given":"Luigi A.","family":"Agrofoglio","sequence":"additional","affiliation":[{"name":"Institute of Organic and Analytical Chemistry, CNRS UMR 7311, Universite d\u2019Orl\u00e9ans, Rue de Chartres, CEDEX 2, 45067 Orleans, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2491-6019","authenticated-orcid":false,"given":"Vincent","family":"Roy","sequence":"additional","affiliation":[{"name":"Institute of Organic and Analytical Chemistry, CNRS UMR 7311, Universite d\u2019Orl\u00e9ans, Rue de Chartres, CEDEX 2, 45067 Orleans, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1093\/femsre\/fuz016","article-title":"Cell wall peptidoglycan in Mycobacterium tuberculosis: An Achilles\u2019 heel for the TB-causing pathogen","volume":"43","author":"Maitra","year":"2019","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1039\/a804532a","article-title":"Recent advances in the formation of the bacterial peptidoglycan monomer unit","volume":"18","year":"2001","journal-title":"Nat. Prod. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1111\/j.1574-6976.2008.00104.x","article-title":"Cytoplasmic steps of peptidoglycan biosynthesis","volume":"32","author":"Barreteau","year":"2008","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/ddr.21465","article-title":"Reaching toward underexplored targets in antibacterial drug design","volume":"80","author":"Gobec","year":"2019","journal-title":"Drug Dev. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/mmi.12758","article-title":"The biology of Mur ligases as an antibacterial target","volume":"94","author":"Kouidmi","year":"2014","journal-title":"Mol. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/499394a","article-title":"Antibiotic resistance: The last resort","volume":"499","author":"McKenna","year":"2013","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.bcp.2016.09.025","article-title":"Antibiotics in late clinical development","volume":"133","author":"Fernandes","year":"2017","journal-title":"Biochem. Pharm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"162","DOI":"10.3109\/03009734.2014.896437","article-title":"Discovery and preclinical development of new antibiotics","volume":"119","author":"Hughes","year":"2014","journal-title":"Upsala J. Med. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.jmb.2006.07.066","article-title":"Structure, function and dynamics in the mur family of bacterial cell wall ligases","volume":"362","author":"Smith","year":"2006","journal-title":"J. Mol. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4905","DOI":"10.1021\/cr200409f","article-title":"Click chemistry for drug development and diverse chemical-biology applications","volume":"113","author":"Thirumurugan","year":"2013","journal-title":"Chem. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3057","DOI":"10.1021\/jo011148j","article-title":"Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(I)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides","volume":"67","author":"Christensen","year":"2002","journal-title":"J. Org. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1002\/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO;2-5","article-title":"Click chemistry: Diverse chemical function from a few good reactions","volume":"40","author":"Kolb","year":"2001","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.carres.2009.01.001","article-title":"Probing replacement of pyrophosphate via click chemistry; synthesis of UPD-sugar analogues as potential glycosyl transferase inhibitors","volume":"344","author":"Butters","year":"2009","journal-title":"Carbohydr. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Yamamoto, I., Sekine, M., and Hata, T. (1980). One-step synthesis of 5\u2019-azido-nucleosides. J. Chem. Soc. Perk. Trans. I, 306\u2013310.","DOI":"10.1039\/P19800000306"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"35134","DOI":"10.1038\/srep35134","article-title":"Development of a one-pot assay for screening and identification of Mur pathway inhibitors in Mycobacterium tuberculosis","volume":"6","author":"Eniyan","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.tube.2009.10.007","article-title":"ATP-dependent MurE ligase in Mycobacterium tuberculosis: Biochemical and structural characterization","volume":"90","author":"Basavannacharya","year":"2010","journal-title":"Tuberculosis"},{"key":"ref_17","unstructured":"DeLano, W.L. (2002). The PyMOL Molecular Graphics System, Delano Scientific."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera-A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1021\/ct700301q","article-title":"GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation","volume":"4","author":"Hess","year":"2008","journal-title":"J. Chem. Theory Comput."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1107\/S0907444904011679","article-title":"PRODRG: A tool for high-throughput crystallography of protein-ligand complexes","volume":"60","author":"Aalten","year":"2004","journal-title":"ACTA Crystallogr. D"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1177\/2472555219881148","article-title":"Screening of Antitubercular Compound Library Identifies Inhibitors of Mur Enzymes in Mycobacterium tuberculosis","volume":"25","author":"Eniyan","year":"2019","journal-title":"SLAS Discov. Adv. Life Sci. R D"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.mib.2003.08.004","article-title":"Novel inhibitors of bacterial cell wall synthesis","volume":"6","author":"Silver","year":"2003","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nrd3975","article-title":"Platforms for antibiotic discovery","volume":"12","author":"Lewis","year":"2003","journal-title":"Nat. Rev. Drug Discov."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/21\/4953\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:28:25Z","timestamp":1760178505000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/21\/4953"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,26]]},"references-count":24,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["molecules25214953"],"URL":"https:\/\/doi.org\/10.3390\/molecules25214953","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,26]]}}}