A Sub-Micromolar MraYAA Inhibitor with an Aminoribosyl Uridine Structure and a (S,S)-Tartaric Diamide: Synthesis, Biological Evaluation and Molecular Modeling.
Oliver, Martin; Le Corre, Laurent; Poinsot, Mélanieet al.
[en] New inhibitors of the bacterial tranferase MraY are described. Their structure is based on an aminoribosyl uridine scaffold, which is known to be important for the biological activity of natural MraY inhibitors. A decyl alkyl chain was introduced onto this scaffold through various linkers. The synthesized compounds were tested against the MraYAA transferase activity, and the most active compound with an original (S,S)-tartaric diamide linker inhibits MraY activity with an IC50 equal to 0.37 µM. Their antibacterial activity was also evaluated on a panel of Gram-positive and Gram-negative strains; however, the compounds showed no antibacterial activity. Docking and molecular dynamics studies revealed that this new linker established two stabilizing key interactions with N190 and H325, as observed for the highly potent inhibitors carbacaprazamycin, muraymycin D2 and tunicamycin.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Oliver, Martin ; Université de Paris, Faculté des Sciences, UMR CNRS 8601, LCBPT, F-75006 Paris, France
Le Corre, Laurent ; Université de Paris, Faculté des Sciences, UMR CNRS 8601, LCBPT, F-75006 Paris, France
Poinsot, Mélanie; Université de Paris, Faculté des Sciences, UMR CNRS 8601, LCBPT, F-75006 Paris, France
Bosco, Michaël ; Université de Paris, Faculté des Sciences, UMR CNRS 8601, LCBPT, F-75006 Paris, France
Wan, Hongwei ; Université de Paris, Faculté des Sciences, UMR CNRS 8601, LCBPT, F-75006 Paris, France
Amoroso, Ana Maria ; Université de Liège - ULiège > Département des sciences de la vie > Centre d'Ingénierie des Protéines (CIP)
Joris, Bernard ; Université de Liège - ULiège > Département des sciences de la vie
Bouhss, Ahmed; Université Paris-Saclay, INSERM U1204, Univ Evry, Structure-Activité des Biomolécules Normales et Pathologiques (SABNP), F-91025 Evry-Courcouronnes, France
Calvet-Vitale, Sandrine ; Université de Paris, Faculté des Sciences, UMR CNRS 8601, LCBPT, F-75006 Paris, France
Gravier-Pelletier, Christine ; Université de Paris, Faculté des Sciences, UMR CNRS 8601, LCBPT, F-75006 Paris, France
Language :
English
Title :
A Sub-Micromolar MraYAA Inhibitor with an Aminoribosyl Uridine Structure and a (S,S)-Tartaric Diamide: Synthesis, Biological Evaluation and Molecular Modeling.
Acknowledgments: We gratefully acknowledge R. Auger and T. Touzé (Institute for Integrative Biology of the Cell (I2BC), CNRS, Université Paris Sud, CEA) for the preparation of the MraY enzyme from Aquifex aeolicus and for their generous gift of the dansylated UDP-MurNAc-pentapeptide used in the enzymatic assays. We warmly thank D. Padovani (CNRS UMR 8601) for his interest in this work and for helpful discussion. The assistance of P. Gerardo (Université de Paris) for low-resolution and high-resolution mass spectra analyses is gratefully acknowledged. We acknowledge the Macromolecular Modelling Platform and the NMR platform core facilities of the BioTechMed facilities INSERM US36|CNRS UMS2009|Université de Paris for docking and MD simulation and NMR experiments, respectively. H.W. thanks the Chinese Scholarship Council for the financial support of her PhD thesis.This research was supported by the ?Centre National de la Recherche Scientifique? and the ?Minist?re de l?Enseignement Sup?rieur et de la Recherche? that also financed M.O.?s PhD grant.We gratefully acknowledge R. Auger and T. Touz? (Institute for Integrative Biology of the Cell (I2BC), CNRS, Universit? Paris Sud, CEA) for the preparation of the MraY enzyme from Aquifex aeolicus and for their generous gift of the dansylated UDP-MurNAc-pentapeptide used in the enzymatic assays. We warmly thank D. Padovani (CNRS UMR 8601) for his interest in this work and for helpful discussion. The assistance of P. Gerardo (Universit? de Paris) for lowresolution and high-resolution mass spectra analyses is gratefully acknowledged. We acknowledge the Macromolecular Modelling Platform and the NMR platform core facilities of the BioTechMed facilities INSERM US36|CNRS UMS2009|Universit? de Paris for docking and MD simulation and NMR experiments, respectively. H.W. thanks the Chinese Scholarship Council for the financial support of her PhD thesis.Funding: This research was supported by the “Centre National de la Recherche Scientifique” and the “Ministère de l’Enseignement Supérieur et de la Recherche” that also financed M.O.’s PhD grant.
Sherry, N.; Howden, B. Emerging Gram negative resistance to last-line antimicrobial agents fosfomycin, colistin and ceftazidimeavibactam—Epidemiology, laboratory detection and treatment implications. Expert Rev. Anti-Infect. Ther. 2018, 16, 289–306. [CrossRef] [PubMed]
Jackson, N.; Czaplewski, L.; Piddock, L.J.V. Discovery and development of new antibacterial drugs: Learning from experience? J. Antimicrob. Chemother. 2018, 73, 1452–1459. [CrossRef] [PubMed]
Van Duijkeren, E.; Schink, A.K.; Roberts, M.C.; Wang, Y.; Schwarz, S. Mechanisms of Bacterial Resistance to Antimicrobial Agents. Microbiol. Spectr. 2018, 6. [CrossRef] [PubMed]
Wozniak, T.M.; Barnsbee, L.; Lee, X.J.; Pacella, R.E. Using the best available data to estimate the cost of antimicrobial resistance: A systematic review. Antimicrob. Resist. Infect. Control 2019, 8, 26. [CrossRef]
Xuemei, Z.; Lundborg, C.S.; Sun, X.; Hu, X.; Dong, H. Economic burden of antibiotic resistance in ESKAPE organisms: A systematic review. Antimicrob. Resist. Infect. Control 2019, 8, 137.
Innes, G.K.; Randad, P.R.; Korinek, A.; Davis, M.F.; Price, L.B.; So, A.D.; Heaney, C.D. External societal costs of antimicrobial resistance in humans attributable to antimicrobial use in livestock. Annu. Rev. Public Health 2020, 41, 141–157. [CrossRef]
Zhen, X.; Li, Y.; Chen, Y.; Dong, P.; Liu, S.; Dong, H. Effect of multiple drug resistance on total medical costs among patients with intra-abdominal infections in China. PLoS ONE 2018, 13, e0193977. [CrossRef]
Liu, Y.; Breukink, E. The membrane steps of bacterial cell wall synthesis as antibiotic targets. Antibiotics 2016, 5, 28. [CrossRef]
Barreteau, H.; Kovač, A.; Boniface, A.; Sova, M.; Gobec, S.; Blanot, D. Cytoplasmic steps of peptidoglycan biosynthesis. FEMS Microbiol. Rev. 2008, 32, 168–207. [CrossRef]
Al-Dabbagh, B.; Olatunji, S.; Crouvoisier, M.; El Ghachi, M.; Blanot, D.; Mengin-Lecreulx, D.; Bouhss, A. Catalytic mechanism of MraY and WecA, two paralogues of the polyprenyl-phosphate N-acetylhexosamine 1-phosphate transferase superfamily. Biochimie 2016, 127, 249–257. [CrossRef]
Falagas, M.E.; Athanasaki, F.; Voulgaris, G.L.; Triarides, N.A.; Vardakas, K.Z. Resistance to fosfomycin: Mechanisms, Frequency and Clinical Consequences. Int. J. Antimicrob. Agents 2019, 53, 22–28. [CrossRef] [PubMed]
Pallares, R.; Liñares, J.; Vadillo, M.; Cabellos, C.; Manresa, F.; Viladrich, P.F.; Martin, R.; Gudiol, F. Resistance to Penicillin and Cephalosporin and Mortality from Severe Pneumococcal Pneumonia in Barcelona, Spain. N. Engl. J. Med. 1995, 333, 474–480. [CrossRef] [PubMed]
Ubukata, M.; Isono, K.; Kimura, K.; Nelson, C.C.; McCloskey, J.A. The structure of liposidomycin B, an inhibitor of bacterial peptidoglycan synthesis. J. Am. Chem. Soc. 1998, 110, 4416–4417. [CrossRef]
Ubukata, M.; Isono, K.; Kimura, K.; Nelson, C.C.; Gregson, J.M.; McCloskey, J.A. Structure elucidation of liposidomycins, a class of complex lipid nucleoside antibiotics. J. Org. Chem. 1992, 57, 6392–6403. [CrossRef]
Brandish, P.E.; Kimura, K.I.; Inukai, M.; Southgate, R.; Lonsdale, J.T.; Bugg, T.D.H. Modes of action of tunicamycin, liposidomycin B, and mureidomycin A: Inhibition of phospho-N-acetylmuramyl-pentapeptide translocase from Escherichia coli. Antimicrob. Agents Chemother. 1996, 40, 1640–1644. [CrossRef]
Igarashi, M.; Nakagawa, N.; Doi, S.; Hattori, N.; Naganawa, H.; Hamada, M. Caprazamycin B, a novel anti-tuberculosis antibiotic, from Streptomyces sp. J. Antibiot. 2003, 56, 580–583. [CrossRef]
Igarashi, M.; Takahashi, Y.; Shitara, T.; Nakamura, H.; Naganawa, H.; Miyake, T.; Akamatsu, Y. Caprazamycins, novel liponucleoside antibiotics, from Streptomyces sp. J. Antibiot. 2005, 58, 327–337. [CrossRef]
Patel, B.; Ryan, P.; Makwana, V.; Zunk, M.; Rudrawar, S.; Grant, G. Caprazamycins: Promising lead structures acting on a novel antibacterial target MraY. Eur. J. Med. Chem. 2019, 171, 462–474. [CrossRef]
Fer, M.J.; Le Corre, L.; Pietrancosta, N.; Evrard-Todeschi, N.; Olatunji, S.; Bouhss, A.; Calvet-Vitale, S.; Gravier-Pelletier, C. Bacterial transferase MraY, a source of inspiration towards new antibiotics. Curr. Med. Chem. 2018, 25, 6013–6025. [CrossRef]
Wiegmann, D.; Koppermann, S.; Wirth, M.; Niro, G.; Leyerer, K.; Ducho, C. Muraymycin nucleoside-peptide antibiotics: Uridinederived natural products as lead structures for the development of novel antibacterial agents. Beilstein J. Org. Chem. 2016, 12, 769–795. [CrossRef] [PubMed]
Ichikawa, S.; Yamaguchi, M.; Matsuda, A. Antibacterial nucleoside natural products inhibiting phospho-MurNAc-pentapeptide translocase; chemistry and structure-activity relationship. Curr. Med. Chem. 2015, 22, 3951–3979. [CrossRef] [PubMed]
Tanino, T.; Ichikawa, S.; Al-Dabbagh, B.; Bouhss, A.; Oyama, H.; Matsuda, A. Synthesis and biological evaluation of muraymycin analogues active against anti-drug-resistant bacteria. ACS Med. Chem. Lett. 2010, 1, 258–262. [CrossRef] [PubMed]
Ichikawa, S.; Yamaguchi, M.; Shang Hsuan, L.; Kato, Y.; Matsuda, A. Carbacaprazamycins: Chemically stable analogues of the caprazamycin nucleoside antibiotics. ACS Infect. Dis. 2015, 1, 151–156. [CrossRef] [PubMed]
Nakaya, T.; Matsuda, A.; Ichikawa, S. Design, synthesis and biological evaluation of 5′-C-piperidinyl-5′-O-aminoribosyluridines as potential antibacterial agents. Org. Biomol. Chem. 2015, 13, 7720–7735. [CrossRef] [PubMed]
Wiegmann, D.; Koppermann, S.; Ducho, C. Aminoribosylated Analogues of Muraymycin Nucleoside Antibiotics. Molecules 2018, 23, 3085. [CrossRef]
Okamoto, K.; Ishikawa, A.; Okawa, R.; Yamamoto, K.; Sato, T.; Yokota, S.-I.; Chiba, K.; Ichikawa, S. Design, synthesis and biological evaluation of simplified analogues of MraY inhibitory natural product with rigid scaffold. Biorg. Med. Chem. 2022, 55, 116556. [CrossRef]
Fer, M.J.; Olatunji, S.; Bouhss, A.; Calvet-Vitale, S.; Gravier-Pelletier, C. Toward analogues of MraY natural inhibitors: Synthesis of 5′-triazole-substitute-aminoribosyl uridines through a Cu-catalyzed azide–alkyne cycloaddition. J. Org. Chem. 2013, 78, 10088–10105. [CrossRef]
Fer, M.J.; Bouhss, A.; Patrão, M.; Le Corre, L.; Pietrancosta, N.; Amoroso, A.; Joris, B.; Mengin-Lecreulx, D.; Calvet-Vitale, S.; Gravier-Pelletier, C. 5′-Methylene-triazole-substituted-aminoribosyl uridines as MraY inhibitors: Synthesis, biological evaluation and molecular modeling. Org. Biomol. Chem. 2015, 13, 7193–7222. [CrossRef]
Chung, B.C.; Mashalidis, E.H.; Tanino, T.; Kim, M.; Matsuda, A.; Hong, J.; Ichikawa, S.; Lee, S.Y. Structural insights into inhibition of lipid I production in bacterial cell wall synthesis. Nature 2016, 533, 557–560. [CrossRef]
Oliver, M.; Le Corre, L.; Poinsot, M.; Corio, A.; Madegard, L.; Bosco, M.; Amoroso, A.; Joris, B.; Auger, R.; Touzé, T.; et al. Synthesis, biological evaluation and molecular modeling of urea-containing MraY inhibitors. Org. Biomol. Chem. 2021, 19, 5844–5866. [CrossRef] [PubMed]
Agnew-Francis, K.A.; Williams, C.M. Squaramides as bioisosteres in contemporary drug design. Chem. Rev. 2020, 120, 11616–11650. [CrossRef] [PubMed]
Canoa, M.E.; Varelaa, O.; García-Morenob, M.I.; García Fernándezc, J.M.; Kovensky, J.; Uhrig, M.L. Synthesis of β Galactosylamides as ligands of the Peanut lectin. Insights into the recognition process. Carbohydr. Res. 2017, 443–444, 58–67. [CrossRef]
Guardiani, C.; Procacci, P. The conformational landscape of tartrate-based inhibitors of the TACE enzyme as revealed by Hamiltonian Replica Exchange simulation. Phys. Chem. Chem. Phys. 2013, 15, 9186–9196. [CrossRef]
Simard, R.D.; Joyal, M.; Gillard, L.; Di Censo, G.; Maharsy, W.L.; Beauregard, J.; Colarusso, P.; Patel, K.D.; Prévost, M.; Nemer, M.; et al. Synthesis of sialyl lewisx glycomimetics bearing a bicyclic 3-O,4-C-fused galactopyranoside scaffold. J. Org. Chem. 2019, 84, 7372–7387. [CrossRef]
Zhao, C.; Rakesh, K.P.; Ravidar, L.; Fang, W.-Y.; Qin, H.-L. Pharmaceutical and medicinal significance of sulfur (SVI)-containing motifs for drug discovery: A critical review. Eur. J. Med. Chem. 2019, 162, 679–734. [CrossRef]
Hirano, S.; Ichikawa, S.; Matsuda, A. Total Synthesis of Caprazol, a Core Structure of the Caprazamycin Antituberculosis Antibiotics. Angew. Chem. Int. 2005, 44, 1854–1856. [CrossRef]
Wu, G.S.; Robertson, D.H.; Brooks, C.L.; Vieth, M. Detailed analysis of grid-based molecular docking: A case study of CDOCKER A CHARMm-based MD docking algorithm. J. Comput. Chem. 2003, 24, 1549–1562. [CrossRef]
Koppermann, S.; Cui, Z.; Fischer, P.D.; Wang, X.; Ludwig, J.; Thorson, J.S.; Van Lanen, S.G.; Ducho, C. Insights into the target interaction of naturally occurring muraymycin nucleoside antibiotics. Chem. Med. Chem. 2018, 13, 779–784. [CrossRef] [PubMed]
Zadeh, S.M.; Astani, E.K.; Wang, Z.-C.; Adhikari, K.; Rattinam, R.; Li, T.-L. Theoretical study of intermolecular interactions between critical residues of membrane protein MraYAA and promising antibiotic muraymycin D2. ACS Omega 2020, 5, 22739–22749. [CrossRef] [PubMed]
Stachyra, T.; Dini, C.; Ferrari, P.; Bouhss, A.; van Heijenoort, J.; Mengin-Lecreulx, D.; Blanot, D.; Bitton, J.; Le Beller, D. Fluorescence detection-based functional assay for high-throughput screening for MraY. Antimicrob. Agents Chemother. 2004, 48, 897–902. [CrossRef]
ISO 20776-1; Clinical Laboratory Testing and In Vitro Diagnostic Test Systems—Susceptibility Testing of Infectious Agents and Evaluation of Performance of Antimicrobial Susceptibility Test Devices—Part 1: Reference Method for Testing the In Vitro Activity of Antimicrobial Agents against Rapidly Growing Aerobic Bacteria Involved in Infectious Diseases. International Organization for Standardization: Geneva, Switzerland, 2006.
Al-Dabbagh, B.; Henry, X.; El Ghachi, M.; Auger, G.; Blanot, D.; Parquet, C.; Mengin-Lecreulx, D.; Bouhss, A. Active site mapping of MraY, a member of the polyprenyl-phosphate N-acetylhexosamine 1-phosphate transferase superfamily, catalyzing the first membrane step of peptidoglycan biosynthesis. Biochemistry 2008, 47, 8919–8928. [CrossRef]
