Catechol-based matrix metalloproteinase inhibitors with additional antioxidative activity

Tauro, Marilena; Laghezza, Antonio; Loiodice, Fulvio; Piemontese, Luca; Caradonna, Alessia; Capelli, Davide; Montanari, R.; Pochetti, G.; Pizio, Antonella Di; Agamennone, Mariangela; Campestre, Cristina; Tortorella, Paolo

doi:10.1080/14756366.2016.1217853

Cited by 27 publications

(33 citation statements)

References 43 publications

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“…As several articles have already described the coordination of metals by pyrazines [44,45], we investigated whether the pyrazine in our compounds could coordinate the Zn 2+ ion in the MMP-8. This could promote potential inhibitory activity on MMP-8, as presented by Tauro et al [43]. We tested this hypothesis using molecular docking studies.…”

Section: Exploring Potential Targets and Activities Using Docking Stumentioning

confidence: 82%

“…We then docked our compound into GTPase KRas, with no interesting results. Finally, matrix metalloproteinase-8 (MMP-8; also known as neutrophil collagenase; PDB ID: 5h8x), was investigated in more detail, where its recently described inhibitors are of the above-mentioned structural type (Ar-SONH 2 -Ar) [43]. This endopeptidase is a part of a very complex proteolytic MMP enzyme family, where its overexpression was linked to several pathological processes [43].…”

Section: Exploring Potential Targets and Activities Using Docking Stumentioning

confidence: 99%

“…Finally, matrix metalloproteinase-8 (MMP-8; also known as neutrophil collagenase; PDB ID: 5h8x), was investigated in more detail, where its recently described inhibitors are of the above-mentioned structural type (Ar-SONH 2 -Ar) [43]. This endopeptidase is a part of a very complex proteolytic MMP enzyme family, where its overexpression was linked to several pathological processes [43]. As several articles have already described the coordination of metals by pyrazines [44,45], we investigated whether the pyrazine in our compounds could coordinate the Zn 2+ ion in the MMP-8.…”

Section: Exploring Potential Targets and Activities Using Docking Stumentioning

confidence: 99%

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Substituted N-(Pyrazin-2-yl)benzenesulfonamides; Synthesis, Anti-Infective Evaluation, Cytotoxicity, and In Silico Studies

et al. 2019

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We prepared a series of substituted N-(pyrazin-2-yl)benzenesulfonamides as an attempt to investigate the effect of different linkers connecting pyrazine to benzene cores on antimicrobial activity when compared to our previous compounds of amide or retro-amide linker type. Only two compounds, 4-amino-N-(pyrazin-2-yl)benzenesulfonamide (MIC = 6.25 µg/mL, 25 µM) and 4-amino-N-(6-chloropyrazin-2-yl)benzenesulfonamide (MIC = 6.25 µg/mL, 22 µM) exerted good antitubercular activity against M. tuberculosis H37Rv. However, they were excluded from the comparison as they-unlike the other compounds-possessed the pharmacophore for the inhibition of folate pathway, which was proven by docking studies. We performed target fishing, where we identified matrix metalloproteinase-8 as a promising target for our title compounds that is worth future exploration.Molecules 2020, 25, 138 2 of 20 several compounds containing a pyrazine core directly connected to a sulfonamide moiety-like in our case-are already documented in the literature with a wide range of pharmacological applications [9]. Examples (Figure 2) include zibotentan, an endothelin receptor antagonist with antitumor activity for prostate cancer [10]; halogenated N-(pyrazinyl)benzenesulfonamides, which are clathrin-coated pit (CCP) chemokine receptor antagonists used in treating chemokine mediated diseases (such as asthma) [11]; and sulfamethoxypyrazine (sulfalene), which is an antibacterial sulfonamide agent [12]. As for antitubercular activity of sulfonamides, a fixed combination of sulfamethoxazole [4-amino-N-(5-methylisoxazol-3-yl)benzenesulfonamide]-trimethoprim [5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4-diamine], also known as co-trimoxazole, has in vitro and in vivo antimycobacterial activity against drug-resistant strains of Mycobacterium tuberculosis (Mtb), and it is used for such cases [13,14]. Sulfamethoxazole is a known inhibitor of bacterial dihydropteroate synthase (DHPS), while trimethoprim is an inhibitor of dihydrofolate reductase (DHFR) [15,16]. Molecules 2020, 25, x 2 of 20 Figure 1. Design rationale: general structure of (a) pyrazinecarboxamides = amides; (b) N-pyrazinylbenzamides = retro-amides; and (c) title compounds = sulfonamides.

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Section: Exploring Potential Targets and Activities Using Docking Stumentioning

confidence: 82%

Section: Exploring Potential Targets and Activities Using Docking Stumentioning

confidence: 99%

Section: Exploring Potential Targets and Activities Using Docking Stumentioning

confidence: 99%

See 1 more Smart Citation

Substituted N-(Pyrazin-2-yl)benzenesulfonamides; Synthesis, Anti-Infective Evaluation, Cytotoxicity, and In Silico Studies

et al. 2019

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“…Research conducted on properties of MMP inhibitors that contain a catechol group in their structures revealed that the catechol oxygens do not coordinate with the zinc ion; they are able to coordinate with zinc ion through one of the oxygen atoms only if they acquire the form of quinone. [ 47 ]…”

Section: Resultsmentioning

confidence: 99%

Interactions between procyanidin oligomers and the active form of matrix metalloproteinase‐7: A theoretical insight

Mendoza–Wilson

Balandrán‐Quintana

2020

Int J of Quantum Chemistry

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The objective of this study was to determine the sites and modes of interaction of the most common oligomers of B‐type procyanidins (PCs) with the active form of the matrix metalloproteinase‐7 (MMP‐7) and some molecular properties of the PCs by using theoretical methods. These data may provide useful insights into the ability of PCs to act as selective MMP‐7 inhibitors. Some stereoisomers that predominated in the analyzed PCs (PB2, PC1, tetramer) could act as selective inhibitors of MMP‐7 due to their interaction with amino acids of the subsites S2 and/or S1′ in the active site, and with some specific amino acids of MMP‐7 that bind to cholesterol sulfate to promote proteolysis of the cell membrane. Hydrogen bonding was the main interaction of PB2 and PC1 with MMP‐7, while in the tetramer, the van der Waals interactions prevailed. The determination of molecular properties such as chemical reactivity and stability by the highest occupied molecular orbital and lowest unoccupied molecular orbital gap, revealed that oligomers of PCs acquired very stable poses in their docking with MMP‐7. Polarizability seems to be an important factor for PCs with large molecular volume (PC1, tetramer) to establish contact with amino acids of narrow subsites in the active site (S2, S1′) and amino acids located outside the active site.

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“…Compared to VMP proteins, MMP proteins has been studied extensively, and many structures exist for MMPs. Close examination of the crystal structure of inhibitor bound MMP8 reveals that the zinc ion in the catalytic site is coordinated by three histidine residues and one catechol inhibitor N-(3,4-dihydroxyphenyl)-4-diphenylsulfonamide 19 . This crystal structure of MMP8 is shown in Figure 1A.…”

Section: Introductionmentioning

confidence: 99%

Computational Analysis of the Metal Selectivity of Matrix Metalloproteinase 8

Long

2020

Preprint

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AbstractMatrix metalloproteinase (MMP) is a class of metalloenzyme that cleaves peptide bonds in extracellular matrices. Their functions are important in both health and disease of animals. Here using quantum mechanics simulations of the MMP8 protein, the coordination chemistry of different metal cofactors is examined. Comparisons found that Jhan-Teller effects in Cu(II) destabilize the wild-type MMP8 but a histidine to glutamine mutation at residue number 197 can potentially allow the MMP8 protein to utilize Cu(II) in reactions. Simulations also demonstrates the requirement of a conformational change in the ligand before enzymatic cleavage. The insights provided in here will assist future protein engineering efforts utilizing the MMP8 protein.

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Catechol-based matrix metalloproteinase inhibitors with additional antioxidative activity

Cited by 27 publications

References 43 publications

Substituted N-(Pyrazin-2-yl)benzenesulfonamides; Synthesis, Anti-Infective Evaluation, Cytotoxicity, and In Silico Studies

Substituted N-(Pyrazin-2-yl)benzenesulfonamides; Synthesis, Anti-Infective Evaluation, Cytotoxicity, and In Silico Studies

Interactions between procyanidin oligomers and the active form of matrix metalloproteinase‐7: A theoretical insight

Computational Analysis of the Metal Selectivity of Matrix Metalloproteinase 8

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