Multivalent MMP-12 inhibitors as a valuable approach to counteract the intestinal epithelial barrier impairment and inflammation in an in vitro model mimicking intestinal high-fat exposure

D’Antongiovanni V, Fornai M, Pellegrini C, Blandizzi C, Antonioli L. Managing obesity and related comorbidities: a potential pharmacological target in the adenosine system? Front Pharmacol. 2021;11:621955.

Jarolimova J, Tagoni J, Stern TA. Obesity: its epidemiology, comorbidities, and management. Prim Care Companion CNS Disord 2013;15:PCC.12f01475. https://doi.org/10.4088/PCC.12f01475.

D’Antongiovanni V, Segnani C, Ippolito C, Antonioli L, Colucci R, Fornai M, et al. Pathological remodeling of the gut barrier as a prodromal event of high-fat diet-induced obesity. Lab Investig. 2023;103:100194. https://doi.org/10.1016/j.labinv.2023.100194.

Article  PubMed  Google Scholar 

D’Antongiovanni V, Pellegrini C, Fornai M, Colucci R, Blandizzi C, Antonioli L, et al. Intestinal epithelial barrier and neuromuscular compartment in health and disease. World J Gastroenterol. 2020;26:1564–79. https://doi.org/10.3748/wjg.v26.i14.1564.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Page-McCaw A, Ewald AJ, Werb Z. Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol. 2007;8:221–33. https://doi.org/10.1038/nrm2125.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cauwe B, Van den Steen PE, Opdenakker G. The biochemical, biological, and pathological kaleidoscope of cell surface substrates processed by matrix metalloproteinases. Crit Rev Biochem Mol Biol. 2007;42:113–85. https://doi.org/10.1080/10409230701340019.

Article  CAS  PubMed  Google Scholar 

Nar H, Werle K, Bauer MM, Dollinger H, Jung B. Crystal structure of human macrophage elastase (MMP-12) in complex with a hydroxamic acid inhibitor. J Mol Biol. 2001;312:743–51. https://doi.org/10.1006/jmbi.2001.4953.

Article  CAS  PubMed  Google Scholar 

Molet S, Belleguic C, Lena H, Germain N, Bertrand CP, Shapiro SD, et al. Increase in macrophage elastase (MMP-12) in lungs from patients with chronic obstructive pulmonary disease. Inflamm Res. 2005;54:31–6. https://doi.org/10.1007/s00011-004-1319-4.

Article  CAS  PubMed  Google Scholar 

McGarry Houghton A. Matrix metalloproteinases in destructive lung disease. Matrix Biol. 2015;44–46:167–74. https://doi.org/10.1016/j.matbio.2015.02.002.

Article  CAS  Google Scholar 

Lagente V, Le Quement C, Boichot E. Macrophage metalloelastase (MMP-12) as a target for inflammatory respiratory diseases. Expert Opin Ther Targets. 2009;13:287–95. https://doi.org/10.1517/14728220902751632.

Article  CAS  PubMed  Google Scholar 

Koppisetti RK, Fulcher YG, Jurkevich A, Prior SH, Xu J, Lenoir M, et al. Ambidextrous binding of cell and membrane bilayers by soluble matrix metalloproteinase-12. Nat Commun. 2014;5:5552 https://doi.org/10.1038/ncomms6552.

Article  CAS  PubMed  Google Scholar 

Li W, Li J, Wu Y, Rancati F, Vallese S, Raveglia L, et al. Identification of an orally efficacious matrix metalloprotease 12 inhibitor for potential treatment of asthma. J Med Chem. 2009;52:5408–19. https://doi.org/10.1021/jm900809r.

Article  CAS  PubMed  Google Scholar 

Nuti E, Cuffaro D, Bernardini E, Camodeca C, Panelli L, Chaves S, et al. Development of thioaryl-based matrix metalloproteinase-12 inhibitors with alternative zinc-binding groups: synthesis, potentiometric, NMR, and crystallographic studies. J Med Chem. 2018;61:4421–35. https://doi.org/10.1021/acs.jmedchem.8b00096.

Article  CAS  PubMed  Google Scholar 

Gona K, Toczek J, Ye Y, Sanzida N, Golbazi A, Boodagh P, et al. Hydroxamate-based selective macrophage elastase (MMP-12) inhibitors and radiotracers for molecular imaging. J Med Chem. 2020;63:15037–49. https://doi.org/10.1021/acs.jmedchem.0c01514.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bordenave T, Helle M, Beau F, Georgiadis D, Tepshi L, Bernes M, et al. Synthesis and in vitro and in vivo evaluation of MMP-12 selective optical probes. Bioconjugate Chem. 2016;27:2407–17. https://doi.org/10.1021/acs.bioconjchem.6b00377.

Article  CAS  Google Scholar 

Butsch V, Börgel F, Galla F, Schwegmann K, Hermann S, Schäfers M, et al. Design, (Radio)synthesis, and in vitro and in vivo evaluation of highly selective and potent matrix metalloproteinase 12 (MMP-12) inhibitors as radiotracers for positron emission tomography. J Med Chem. 2018;61:4115–34. https://doi.org/10.1021/acs.jmedchem.8b00200.

Article  CAS  PubMed  Google Scholar 

Niu H, Li Y, Li H, Chi Y, Zhuang M, Zhang T, et al. Matrix metalloproteinase 12 modulates high-fat-diet induced glomerular fibrogenesis and inflammation in a mouse model of obesity. Sci Rep. 2016;6:20171. https://doi.org/10.1038/srep20171.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nighot M, Ganapathy AS, Saha K, Suchanec E, Castillo EF, Gregory A, et al. Matrix metalloproteinase MMP-12 promotes macrophage transmigration across intestinal epithelial tight junctions and increases severity of experimental colitis. J Crohns Colitis. 2021;15:1751–65. https://doi.org/10.1093/ecco-jcc/jjab064.

Article  PubMed  PubMed Central  Google Scholar 

Evans HM, Schultz DF, Boiman AJ, McKell MC, Qualls JE, Deepe GS. Restraint of fumarate accrual by HIF-1α preserves miR-27a-mediated limitation of interleukin 10 during infection of macrophages by Histoplasma Capsulatum. mBio. 2021;12:e0271021. https://doi.org/10.1128/mBio.02710-21.

Article  PubMed  Google Scholar 

Song M, Zhang S, Tao Z, Li J, Shi Y, Xiong Y, et al. MMP-12 siRNA improves the homeostasis of the small intestine and metabolic dysfunction in high-fat diet feeding-induced obese mice. Biomaterials. 2021;278:121183 https://doi.org/10.1016/j.biomaterials.2021.121183.

Article  CAS  PubMed  Google Scholar 

Nuti E, Cuffaro D, D’Andrea F, Rosalia L, Tepshi L, Fabbi M, et al. Sugar-based arylsulfonamide carboxylates as selective and water-soluble matrix metalloproteinase-12 inhibitors. ChemMedChem. 2016;11:1626–37. https://doi.org/10.1002/cmdc.201600235.

Article  CAS  PubMed  Google Scholar 

Cuffaro D, Camodeca C, D’Andrea F, Piragine E, Testai L, Calderone V, et al. Matrix metalloproteinase-12 inhibitors: synthesis, structure-activity relationships and intestinal absorption of novel sugar-based biphenylsulfonamide carboxylates. Bioorg Med Chem. 2018;26:5804–15. https://doi.org/10.1016/j.bmc.2018.10.024.

Article  CAS  PubMed  Google Scholar 

Dorel R, Wong AR, Crawford JJ. Trust your gut: strategies and tactics for intestinally restricted drugs. ACS Med Chem Lett. 2023;14:233–43. https://doi.org/10.1021/acsmedchemlett.3c00001.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Flipo M, Charton J, Hocine A, Dassonneville S, Deprez B, Deprez-Poulain R. Hydroxamates: relationships between structure and plasma stability. J Med Chem. 2009;52:6790–802. https://doi.org/10.1021/jm900648x.

Article  CAS  PubMed  Google Scholar 

Nuti E, Rosalia L, Cuffaro D, Camodeca C, Giacomelli C, Da Pozzo E, et al. Bifunctional inhibitors as a new tool to reduce cancer cell invasion by impairing MMP-9 homodimerization. ACS Med Chem Lett. 2017;8:293–8. https://doi.org/10.1021/acsmedchemlett.6b00446.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nuti E, Rossello A, Cuffaro D, Camodeca C, Van Bael J, van der Maat D, et al. Bivalent inhibitor with selectivity for trimeric MMP-9 amplifies neutrophil chemotaxis and enables functional studies on MMP-9 proteoforms. Cells. 2020;9:E1634. https://doi.org/10.3390/cells9071634.

Article  CAS  Google Scholar 

Antoni C, Vera L, Devel L, Catalani MP, Czarny B, Cassar-Lajeunesse E, et al. Crystallization of bi-functional ligand protein complexes. J Struct Biol. 2013;182:246–54. https://doi.org/10.1016/j.jsb.2013.03.015.

Article  CAS  PubMed  Google Scholar 

Kramer W, Glombik H. Bile acid reabsorption inhibitors (BARI): novel hypolipidemic drugs. Curr Med Chem. 2006;13:997–1016. https://doi.org/10.2174/092986706776361003.

Article  CAS  PubMed  Google Scholar 

Akocak S, Alam MR, Shabana AM, Sanku RKK, Vullo D, Thompson H, et al. PEGylated bis-sulfonamide carbonic anhydrase inhibitors can efficiently control the growth of several carbonic anhydrase IX-expressing carcinomas. J Med Chem. 2016;59:5077–88. https://doi.org/10.1021/acs.jmedchem.6b00492.

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