{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:22:23Z","timestamp":1783056143667,"version":"3.54.6"},"reference-count":107,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T00:00:00Z","timestamp":1604966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007514","name":"University of Pisa","doi-asserted-by":"publisher","award":["PRA_2018_20"],"award-info":[{"award-number":["PRA_2018_20"]}],"id":[{"id":"10.13039\/501100007514","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Matrix metalloproteinases (MMPs) and A disintegrin and Metalloproteinase (ADAMs) are zinc-dependent endopeptidases belonging to the metzincin superfamily. Upregulation of metzincin activity is a major feature in many serious pathologies such as cancer, inflammations, and infections. In the last decades, many classes of small molecules have been developed directed to inhibit these enzymes. The principal shortcomings that have hindered clinical development of metzincin inhibitors are low selectivity for the target enzyme, poor water solubility, and long-term toxicity. Over the last 15 years, a novel approach to improve solubility and bioavailability of metzincin inhibitors has been the synthesis of carbohydrate-based compounds. This strategy consists of linking a hydrophilic sugar moiety to an aromatic lipophilic scaffold. This review aims to describe the development of sugar-based and azasugar-based derivatives as metzincin inhibitors and their activity in several pathological models.<\/jats:p>","DOI":"10.3390\/ph13110376","type":"journal-article","created":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T10:47:28Z","timestamp":1605005248000},"page":"376","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Developments in Carbohydrate-Based Metzincin Inhibitors"],"prefix":"10.3390","volume":"13","author":[{"given":"Doretta","family":"Cuffaro","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Pisa, via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2669-5376","authenticated-orcid":false,"given":"Elisa","family":"Nuti","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1517-4911","authenticated-orcid":false,"given":"Felicia","family":"D\u2019Andrea","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6795-8091","authenticated-orcid":false,"given":"Armando","family":"Rossello","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/0014-5793(93)80312-I","article-title":"Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc-binding environments (HEXXHXXGXXH and Met-turn) and topologies and should be grouped into a common family, the \u2018metzincins\u2019","volume":"331","author":"Bode","year":"1993","journal-title":"FEBS Lett."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13951","DOI":"10.1074\/jbc.M109.083378","article-title":"On the Relevance of the Met-turn Methionine in Metzincins","volume":"285","author":"Tallant","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/nrd4390","article-title":"Is there new hope for therapeutic matrix metalloproteinase inhibition?","volume":"13","author":"Vandenbroucke","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.mam.2008.05.002","article-title":"Progress in matrix metalloproteinase research","volume":"29","author":"Murphy","year":"2008","journal-title":"Mol. Asp. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.biochi.2004.11.019","article-title":"Crystal structures of MMPs in complex with physiological and pharmacological inhibitors","volume":"87","author":"Maskos","year":"2005","journal-title":"Biochimie"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1107\/S2053230X13034857","article-title":"Crystallization and preliminary X-ray crystallographic analysis of the catalytic domain of membrane type 1 matrix metalloproteinase","volume":"70","author":"Ogata","year":"2014","journal-title":"Acta Crystallogr. Sect. F Struct. Biol. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.bbamcr.2009.04.003","article-title":"Matrix metalloproteinases: Fold and function of their catalytic domains","volume":"1803","author":"Tallant","year":"2010","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5334","DOI":"10.1073\/pnas.0407106102","article-title":"Conformational variability of matrix metalloproteinases: Beyond a single 3D structure","volume":"102","author":"Bertini","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nrm2125","article-title":"Matrix metalloproteinases and the regulation of tissue remodelling","volume":"8","author":"Ewald","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1016\/0006-291X(72)90076-9","article-title":"On the size of the active site in proteases: Pronase","volume":"46","author":"Schechter","year":"1972","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_11","first-page":"35","article-title":"Specificity of Binding with Matrix Metalloproteinases","volume":"103","author":"Gupta","year":"2012","journal-title":"Exp. Suppl."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.drudis.2019.07.013","article-title":"Understanding the variability of the S1\u2032 pocket to improve matrix metalloproteinase inhibitor selectivity profiles","volume":"25","author":"Gimeno","year":"2020","journal-title":"Drug Discov. Today"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.mam.2008.08.001","article-title":"The ADAM metalloproteinases","volume":"29","author":"Edwards","year":"2008","journal-title":"Mol. Asp. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Giebeler, N., and Zigrino, P. (2016). A Disintegrin and Metalloprotease (ADAM): Historical Overview of Their Functions. Toxins, 8.","DOI":"10.3390\/toxins8040122"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1101\/gad.1039703","article-title":"The ADAMs family of metalloproteases: Multidomain proteins with multiple functions","volume":"17","author":"Seals","year":"2003","journal-title":"Genes Dev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1107\/S1744309112015618","article-title":"Structure of human ADAM-8 catalytic domain complexed with batimastat","volume":"68","author":"Hall","year":"2012","journal-title":"Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1016\/j.cell.2017.11.014","article-title":"Structural Basis for Regulated Proteolysis by the \u03b1-Secretase ADAM10","volume":"171","author":"Seegar","year":"2017","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3408","DOI":"10.1073\/pnas.95.7.3408","article-title":"Crystal structure of the catalytic domain of human tumor necrosis factor-\u03b1-converting enzyme","volume":"95","author":"Maskos","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jmb.2003.10.037","article-title":"Crystal Structure of the Catalytic Domain of Human ADAM33","volume":"335","author":"Orth","year":"2004","journal-title":"J. Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1023\/A:1020692710029","article-title":"Structure\u2013Function Analysis of the ADAM Family of Disintegrin-Like and Metalloproteinase-Containing Proteins (Review)","volume":"18","author":"Stone","year":"1999","journal-title":"J. Protein Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3693","DOI":"10.1242\/dev.076398","article-title":"Ectodomain shedding and ADAMs in development","volume":"139","author":"Weber","year":"2012","journal-title":"Development"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1038\/nrc2459","article-title":"The ADAMs: Signalling scissors in the tumour microenvironment","volume":"8","author":"Murphy","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_23","first-page":"75","article-title":"Matrix metalloproteinase protein inhibitors: Highlighting a new beginning for metalloproteinases in medicine","volume":"3","author":"Boucher","year":"2016","journal-title":"Met. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1158\/1535-7163.MCT-17-0646","article-title":"Matrix Metalloproteinase Inhibitors in Cancer Therapy: Turning Past Failures into Future Successes","volume":"17","author":"Winer","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1016\/j.bbagen.2014.03.007","article-title":"Matrix metalloproteinases in inflammation","volume":"1840","author":"Nissinen","year":"2014","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/nrd2308","article-title":"Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases","volume":"6","author":"Hu","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3097","DOI":"10.1007\/s00018-019-03174-6","article-title":"MMPs and ADAMs in neurological infectious diseases and multiple sclerosis","volume":"76","author":"Muri","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"138","DOI":"10.3389\/fcimb.2017.00138","article-title":"Ectodomain Shedding by ADAM17: Its Role in Neutrophil Recruitment and the Impairment of This Process during Sepsis","volume":"7","author":"Mishra","year":"2017","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1007\/s00018-019-03178-2","article-title":"Metalloproteinases and their tissue inhibitors in Alzheimer\u2019s disease and other neurodegenerative disorders","volume":"76","author":"Rivera","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1080\/14728222.2017.1386176","article-title":"ADAM10 as a therapeutic target for brain diseases: From developmental disorders to Alzheimer\u2019s disease","volume":"21","author":"Marcello","year":"2017","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s10571-015-0232-4","article-title":"The Distinct Role of ADAM17 in APP Proteolysis and Microglial Activation Related to Alzheimer\u2019s Disease","volume":"36","author":"Qian","year":"2016","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7960","DOI":"10.1002\/chem.201805361","article-title":"Design and Structural Evolution of Matrix Metalloproteinase Inhibitors","volume":"25","author":"Fischer","year":"2019","journal-title":"Chem. Eur. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s10555-006-7894-9","article-title":"Recent advances in MMP inhibitor design","volume":"25","author":"Fisher","year":"2006","journal-title":"Cancer Metastasis Rev."},{"key":"ref_34","first-page":"137","article-title":"Hydroxamic Acids as Matrix Metalloproteinase Inhibitors","volume":"103","author":"Verma","year":"2012","journal-title":"Exp. Suppl."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1021\/cr9804543","article-title":"Design and Therapeutic Application of Matrix Metalloproteinase Inhibitors","volume":"99","author":"Whittaker","year":"1999","journal-title":"Chem. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1021\/jm960871c","article-title":"Discovery of CGS 27023A, a Non-Peptidic, Potent, and Orally Active Stromelysin Inhibitor That Blocks Cartilage Degradation in Rabbits","volume":"40","author":"MacPherson","year":"1997","journal-title":"J. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.jmb.2003.12.033","article-title":"Crystal Structure of the Catalytic Domain of Human Matrix Metalloproteinase 10","volume":"336","author":"Bertini","year":"2004","journal-title":"J. Mol. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1016\/j.bmc.2004.01.047","article-title":"New N-arylsulfonyl-N-alkoxyaminoacetohydroxamic acids as selective inhibitors of gelatinase A (MMP-2)","volume":"12","author":"Rossello","year":"2004","journal-title":"Bioorganic Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1016\/j.bbamcr.2017.06.009","article-title":"Next generation matrix metalloproteinase inhibitors\u2014Novel strategies bring new prospects","volume":"1864","author":"Levin","year":"2017","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1002\/art.11030","article-title":"Broad-spectrum matrix metalloproteinase inhibitor marimastat-induced musculoskeletal side effects in rats","volume":"48","author":"Renkiewicz","year":"2003","journal-title":"Arthritis Rheum."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9585","DOI":"10.1021\/acs.jmedchem.7b01001","article-title":"Targeted Polypharmacology: Discovery of a Highly Potent Non-Hydroxamate Dual Matrix Metalloproteinase (MMP)-10\/-13 Inhibitor","volume":"60","author":"Senn","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8886","DOI":"10.1021\/jm500981k","article-title":"Discovery of Novel, Highly Potent, and Selective Quinazoline-2-carboxamide-Based Matrix Metalloproteinase (MMP)-13 Inhibitors without a Zinc Binding Group Using a Structure-Based Design Approach","volume":"57","author":"Nara","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5816","DOI":"10.1021\/acs.jmedchem.7b00514","article-title":"Structure-Based Design and Synthesis of Potent and Selective Matrix Metalloproteinase 13 Inhibitors","volume":"60","author":"Choi","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4977","DOI":"10.1158\/0008-5472.CAN-10-4552","article-title":"Small-Molecule Anticancer Compounds Selectively Target the Hemopexin Domain of Matrix Metalloproteinase-9","volume":"71","author":"Dufour","year":"2011","journal-title":"Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1158\/0008-5472.CAN-11-4149","article-title":"Novel MT1-MMP Small-Molecule Inhibitors Based on Insights into Hemopexin Domain Function in Tumor Growth","volume":"72","author":"Remacle","year":"2012","journal-title":"Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"9598","DOI":"10.1021\/jm501284e","article-title":"Characterization of Selective Exosite-Binding Inhibitors of Matrix Metalloproteinase 13 That Prevent Articular Cartilage Degradation In Vitro","volume":"57","author":"Spicer","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.ejcb.2010.11.005","article-title":"The \u201cA Disintegrin and Metalloproteases\u201d ADAM10 and ADAM17: Novel drug targets with therapeutic potential?","volume":"90","author":"Saftig","year":"2011","journal-title":"Eur. J. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1016\/j.bbamcr.2017.07.001","article-title":"The shedding protease ADAM17: Physiology and pathophysiology","volume":"1864","author":"Zunke","year":"2017","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1158\/1078-0432.CCR-06-2116","article-title":"Selective Inhibition of ADAM Metalloproteases as a Novel Approach for Modulating ErbB Pathways in Cancer","volume":"13","author":"Fridman","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ccr.2006.05.024","article-title":"Targeting ADAM-mediated ligand cleavage to inhibit HER3 and EGFR pathways in non-small cell lung cancer","volume":"10","author":"Zhou","year":"2006","journal-title":"Cancer Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"8089","DOI":"10.1021\/jm4011753","article-title":"Selective Arylsulfonamide Inhibitors of ADAM-17: Hit Optimization and Activity in Ovarian Cancer Cell Models","volume":"56","author":"Nuti","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"36473","DOI":"10.1074\/jbc.M112.389114","article-title":"Discovery of Novel Inhibitors of a Disintegrin and Metalloprotease 17 (ADAM17) Using Glycosylated and Non-glycosylated Substrates","volume":"287","author":"Minond","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5808","DOI":"10.1021\/acs.jmedchem.5b00354","article-title":"SAR Studies of Exosite-Binding Substrate-Selective Inhibitors of A Disintegrin And Metalloprotease 17 (ADAM17) and Application as Selective in Vitro Probes","volume":"58","author":"Knapinska","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.2174\/138161207781039706","article-title":"Matrix Metalloproteinase Inhibitors: New Challenges in the Era of Post Broad-Spectrum Inhibitors","volume":"13","author":"Nuti","year":"2007","journal-title":"Curr. Pharm. Des."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.2174\/0929867325666180326164104","article-title":"ADAM Metalloproteinases as Potential Drug Targets","volume":"26","author":"Camodeca","year":"2019","journal-title":"Curr. Med. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ejmech.2014.03.064","article-title":"Study of the binding interaction between fluorinated matrix metalloproteinase inhibitors and Human Serum Albumin","volume":"79","author":"Digilio","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_57","unstructured":"Gabius, H.-J. (2009). The Sugar Code. Fundamentals of Glycosciences, Wiley-VCH."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Ernst, B., Hart, G.W., and Sina\u00fd, P. (2000). Carbohydrates in Chemistry and Biology, Wiley-VCH.","DOI":"10.1002\/9783527618255"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1039\/C9ME00175A","article-title":"Potentiating anti-cancer chemotherapeutics and antimicrobials via sugar-mediated strategies","volume":"5","author":"Mullapudi","year":"2020","journal-title":"Mol. Syst. Des. Eng."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1093\/femsre\/fuy011","article-title":"Potential targets for next generation antimicrobial glycoconjugate vaccines","volume":"42","author":"Micoli","year":"2018","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Khatun, F., Toth, I., and Stephenson, R.J. (2020). Immunology of carbohydrate-based vaccines. Adv. Drug Deliv. Rev.","DOI":"10.1016\/j.addr.2020.04.006"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12929-019-0591-0","article-title":"Synthetic carbohydrate-based vaccines: Challenges and opportunities","volume":"27","author":"Mettu","year":"2020","journal-title":"J. Biomed. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Gragnani, T., Cuffaro, D., Fallarini, S., Lombardi, G., D\u2019Andrea, F., and Guazzelli, L. (2019). Selectively Charged and Zwitterionic Analogues of the Smallest Immunogenic Structure of Streptococcus Pneumoniae Type 14. Molecules, 24.","DOI":"10.3390\/molecules24183414"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Hossain, F., and Andreana, P.R. (2019). Developments in Carbohydrate-Based Cancer Therapeutics. Pharmaceuticals, 12.","DOI":"10.3390\/ph12020084"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"D\u2019Andrea, F., Vagelli, G., Granchi, C., Guazzelli, L., Tuccinardi, T., Poli, G., Iacopini, D., Minutolo, F., and Di Bussolo, V. (2019). Synthesis and Biological Evaluation of New Glycoconjugated LDH Inhibitors as Anticancer Agents. Molecules, 24.","DOI":"10.3390\/molecules24193520"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"633","DOI":"10.2174\/1389557033487737","article-title":"Aspects of the stability and bioavailability of carbohydrates and carbohydrate derivatives","volume":"3","author":"Drinnan","year":"2003","journal-title":"Mini Revi. Med. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2733","DOI":"10.2174\/0929867033456413","article-title":"Recent Developments in the Synthesis and Discovery of Oligosaccharides and Glycoconjugates for the Treatment of Disease","volume":"10","author":"Macmillan","year":"2003","journal-title":"Curr. Med. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1124\/jpet.119.263657","article-title":"Glycoconjugation as a Promising Treatment Strategy for Psoriasis","volume":"373","author":"Makuch","year":"2020","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"110","DOI":"10.5306\/wjco.v11.i3.110","article-title":"Glycoconjugation: An approach to cancer therapeutics","volume":"11","author":"Molejon","year":"2020","journal-title":"World J. Clin. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Cuffaro, D., Nuti, E., and Rossello, A. (2020). An overview of carbohydrate-based Carbonic Anhydrase inhibitors. J. Enzyme Inhib. Med. Chem.","DOI":"10.1080\/14756366.2020.1825409"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Jimenez-Barbero, J., Canada, F.J., and Martin-Santamaria, S. (2015). Carbohydrate-containing matrix metalloproteinase inhibitors. Carbohydrates in Drug Design and Discovery, RSC Drug Discovery.","DOI":"10.1039\/9781849739993"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1002\/cbic.200400456","article-title":"Design In Silico, Synthesis and Binding Evaluation of a Carbohydrate-Based Scaffold for Structurally Novel Inhibitors of Matrix Metalloproteinases","volume":"6","author":"Fragai","year":"2005","journal-title":"ChemBioChem"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1002\/cmdc.200600020","article-title":"A High-Affinity Carbohydrate-Containing Inhibitor of Matrix Metalloproteinases","volume":"1","author":"Calderone","year":"2006","journal-title":"ChemMedChem"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1002\/chem.201203794","article-title":"Targeting Matrix Metalloproteinases: Design of a Bifunctional Inhibitor for Presentation by Tumour-Associated Galectins","volume":"19","author":"Bartoloni","year":"2012","journal-title":"Chem. A Eur. J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4714","DOI":"10.1021\/jm300199g","article-title":"A New Class of Highly Potent Matrix Metalloproteinase Inhibitors Based on Triazole-Substituted Hydroxamates: (Radio)Synthesis and in Vitro and First in Vivo Evaluation","volume":"55","author":"Hugenberg","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1002\/cmdc.201600235","article-title":"Sugar-Based Arylsulfonamide Carboxylates as Selective and Water-Soluble Matrix Metalloproteinase-12 Inhibitors","volume":"11","author":"Nuti","year":"2016","journal-title":"ChemMedChem"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5804","DOI":"10.1016\/j.bmc.2018.10.024","article-title":"Matrix metalloproteinase-12 inhibitors: Synthesis, structure-activity relationships and intestinal absorption of novel sugar-based biphenylsulfonamide carboxylates","volume":"26","author":"Cuffaro","year":"2018","journal-title":"Bioorganic Med. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.bcp.2012.06.026","article-title":"N-O-Isopropyl sulfonamido-based hydroxamates: Kinetic characterisation of a series of MMP-12\/MMP-13 dual target inhibitors","volume":"84","author":"Santamaria","year":"2012","journal-title":"Biochem. Pharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4421","DOI":"10.1021\/acs.jmedchem.8b00096","article-title":"Development of Thioaryl-Based Matrix Metalloproteinase-12 Inhibitors with Alternative Zinc-Binding Groups: Synthesis, Potentiometric, NMR, and Crystallographic Studies","volume":"61","author":"Nuti","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1002\/cmdc.201800733","article-title":"Design and Synthesis of Ionic Liquid-Based Matrix Metalloproteinase Inhibitors (MMPIs): A Simple Approach to Increase Hydrophilicity and to Develop MMPI-Coated Gold Nanoparticles","volume":"14","author":"Nuti","year":"2019","journal-title":"ChemMedChem"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"6347","DOI":"10.1021\/jm900335a","article-title":"Design, Synthesis, Biological Evaluation, and NMR Studies of a New Series of Arylsulfones As Selective and Potent Matrix Metalloproteinase-12 Inhibitors","volume":"52","author":"Nuti","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.jsb.2013.03.015","article-title":"Crystallization of bi-functional ligand protein complexes","volume":"182","author":"Antoni","year":"2013","journal-title":"J. Struct. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"E141","DOI":"10.1152\/ajpendo.00712.2009","article-title":"Glucose transporters in the 21st Century","volume":"298","author":"Thorens","year":"2010","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.carbpol.2016.02.022","article-title":"Hyaluronic acid based hydroxamate and conjugates with biologically active amines: In vitro effect on matrix metalloproteinase-2","volume":"144","author":"Gaskarova","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Compain, P., and Martin, O.R. (2007). Iminosugars: From Synthesis to Therapeutic Applications, Wiley-VCH.","DOI":"10.1002\/9780470517437"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"460","DOI":"10.3184\/174751917X15000341607489","article-title":"Synthesis of 1-Deoxynojirimycin: Exploration of Optimised Conditions for Reductive Amidation and Separation of Epimers","volume":"41","author":"Iftikhar","year":"2017","journal-title":"J. Chem. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"6812","DOI":"10.1002\/ejoc.201800943","article-title":"Synthetic Pathways to 3,4,5-Trihydroxypiperidines from the Chiral Pool","volume":"2018","author":"Wood","year":"2018","journal-title":"Eur. J. Org. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"107744","DOI":"10.1016\/j.carres.2019.107744","article-title":"Preparation of 1,6-di-deoxy-d-galacto and 1,6-di-deoxy-l-altro nojirimycin derivatives by aminocyclization of a 1,5-dicarbonyl derivative","volume":"482","author":"Cuffaro","year":"2019","journal-title":"Carbohydr. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4765","DOI":"10.1002\/ejoc.201900605","article-title":"C -Branched Imino Sugars: Synthesis and Biological Relevance","volume":"2019","year":"2019","journal-title":"Eur. J. Org. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/j.tetasy.2005.02.020","article-title":"Recent advances in the chemistry of azapyranose sugars","volume":"16","author":"Afarinkia","year":"2005","journal-title":"Tetrahedron Asymmetry"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"6527","DOI":"10.1002\/ejoc.201402555","article-title":"Stereoselective Access to the \u03b2-D-N-Acetylhexosaminyl-(1\u21924)-1-deoxy-D-nojirimycin Disaccharide Series Avoiding the Glycosylation Reaction","volume":"2014","author":"Guazzelli","year":"2014","journal-title":"Eur. J. Org. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"103298","DOI":"10.1016\/j.bioorg.2019.103298","article-title":"Synthesis and investigation of polyhydroxylated pyrrolidine derivatives as novel chemotypes showing dual activity as glucosidase and aldose reductase inhibitors","volume":"92","author":"Guazzelli","year":"2019","journal-title":"Bioorganic Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.tibtech.2008.12.003","article-title":"Glycosidases: A key to tailored carbohydrates","volume":"27","year":"2009","journal-title":"Trends Biotechnol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.drudis.2010.08.017","article-title":"Iminosugars past, present and future: Medicines for tomorrow","volume":"16","author":"Horne","year":"2011","journal-title":"Drug Discov. Today"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Gao, K., Zheng, C., Wang, T., Zhao, H., Wang, J., Wang, Z., Zhai, X., Jia, Z., Chen, J., and Zhou, Y. (2016). 1-Deoxynojirimycin: Occurrence, Extraction, Chemistry, Oral Pharmacokinetics, Biological Activities and In Silico Target Fishing. Molecules, 21.","DOI":"10.3390\/molecules21111600"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Junge, B., Matzke, M., and Stoltefuss, J. (1996). Chemistry and Structure\u2014Activity Relationships of Glucosidase Inhibitors. Handbook of Experimental Pharmacology, Springer.","DOI":"10.1007\/978-3-662-09127-2_15"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1345\/aph.19269","article-title":"Miglitol: Assessment of its role in the treatment of patients with diabetes mellitus","volume":"34","author":"Campbell","year":"2000","journal-title":"Ann. Pharmacother."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1046\/j.1463-1326.2002.00219.x","article-title":"The effects of miglitol on glucagon-like peptide-1 secretion and appetite sensations in obese type 2 diabetics","volume":"4","author":"Lee","year":"2002","journal-title":"Diabetes Obes. Metab."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.bcmd.2016.10.017","article-title":"Twelve years of experience with miglustat in the treatment of type 1 Gaucher disease: The Spanish ZAGAL project","volume":"68","author":"Giraldo","year":"2018","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"8988","DOI":"10.1021\/jf101401b","article-title":"1-Deoxynojirimycin Inhibits Metastasis of B16F10 Melanoma Cells by Attenuating the Activity and Expression of Matrix Metalloproteinases-2 and -9 and Altering Cell Surface Glycosylation","volume":"58","author":"Wang","year":"2010","journal-title":"J. Agric. Food Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"9867","DOI":"10.1021\/jf403636z","article-title":"Mulberry 1-Deoxynojirimycin Pleiotropically Inhibits Glucose-Stimulated Vascular Smooth Muscle Cell Migration by Activation of AMPK\/RhoB and Down-regulation of FAK","volume":"61","author":"Chan","year":"2013","journal-title":"J. Agric. Food Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1016\/S0960-894X(03)00530-4","article-title":"Structure\u2013activity relationships of azasugar-based MMP\/ADAM inhibitors","volume":"13","author":"Moriyama","year":"2003","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.1016\/S0960-894X(03)00531-6","article-title":"Design, synthesis and evaluation of novel azasugar-based MMP\/ADAM inhibitors","volume":"13","author":"Moriyama","year":"2003","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1021\/jm0304313","article-title":"Azasugar-Based MMP\/ADAM Inhibitors as Antipsoriatic Agents","volume":"47","author":"Moriyama","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"140","DOI":"10.2174\/156720209788970072","article-title":"CB-12181, a New Azasugar-Based Matrix Metalloproteinase\/Tumor Necrosis Factor-\u03b1 Converting Enzyme Inhibitor, Inhibits Vascular Endothelial Growth Factor-Induced Angiogenesis in Vitro and Retinal Neovascularization in Vivo","volume":"6","author":"Chikaraishi","year":"2009","journal-title":"Curr. Neurovascular Res."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Sylte, I., Dawadi, R., Malla, N., Von Hofsten, S., Nguyen, T.-M., Solli, A.I., Berg, E., Adekoya, O.A., Svineng, G., and Winberg, J.-O. (2018). The selectivity of galardin and an azasugar-based hydroxamate compound for human matrix metalloproteases and bacterial metalloproteases. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0200237"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1016\/j.bmcl.2003.12.091","article-title":"Synthesis and biological activity of selective azasugar-based TACE inhibitors","volume":"14","author":"Tsukida","year":"2004","journal-title":"Bioorganic Med. Chem. Lett."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/13\/11\/376\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:31:43Z","timestamp":1760178703000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/13\/11\/376"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,10]]},"references-count":107,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["ph13110376"],"URL":"https:\/\/doi.org\/10.3390\/ph13110376","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,10]]}}}