Synthesis and discovery of (I-3,II-3)-biacacetin as a novel non-zinc binding inhibitor of MMP-2 and MMP-9

Nanjan, Pandurangan; Nambiar, Jyotsna; Nair, Bipin; Banerji, Asoke

doi:10.1016/j.bmc.2015.03.084

Cited by 27 publications

(11 citation statements)

References 12 publications

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“…Thus, molecular dynamics (MD) simulations were carried out to include the effects of induced fit and the interaction with explicit water molecules into the binding model. In particular, we focused on MMP-2, as it is an important therapeutic target, and just a few NZIs have been identified so far [28,36,37]. The binding of the above-mentioned 1h and 1i ligands was studied, being representative of the case of highly similar ligands characterized by highly different inhibition activities.…”

Section: Resultsmentioning

confidence: 99%

“…While MMP-13 NZIs have been widely investigated [25], there are only a few examples of MMP-2 non-zinc-binding ligands [28,36,37]; therefore, our focus was to depict the binding process of newly-designed inhibitors, gaining more insight into the essential structural features for MMP-2 non-zinc binding inhibition, in order to drive the design of the selective and most potent ligands.…”

Section: Discussionmentioning

confidence: 99%

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Seeking for Non-Zinc-Binding MMP-2 Inhibitors: Synthesis, Biological Evaluation and Molecular Modelling Studies

Ammazzalorso

Filippis

Campestre

et al. 2016

IJMS

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Matrix metalloproteinases (MMPs) are an important family of zinc-containing enzymes with a central role in many physiological and pathological processes. Although several MMP inhibitors have been synthesized over the years, none reached the market because of off-target effects, due to the presence of a zinc binding group in the inhibitor structure. To overcome this problem non-zinc-binding inhibitors (NZIs) have been recently designed. In a previous article, a virtual screening campaign identified some hydroxynaphtyridine and hydroxyquinoline as MMP-2 non-zinc-binding inhibitors. In the present work, simplified analogues of previously-identified hits have been synthesized and tested in enzyme inhibition assays. Docking and molecular dynamics studies were carried out to rationalize the activity data.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Seeking for Non-Zinc-Binding MMP-2 Inhibitors: Synthesis, Biological Evaluation and Molecular Modelling Studies

Ammazzalorso

Filippis

Campestre

et al. 2016

IJMS

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“…Twenty compounds were selected for purchase and the subsequent enzymatic assay. The selected compounds were not similar to the published non-zinc binding MMP-2 inhibitors [28][29][30][31][32].…”

Section: Visual Inspection and Final Selection Of The Hits For Purchasementioning

confidence: 87%

Identification of Non-Zinc Binding Inhibitors of MMP-2 Through Virtual Screening and Subsequent Rescoring

Shamsara

2018

Drug Res (Stuttg)

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MMP-2 belongs to a large family of proteases called matrix metalloproteinases (MMPs) that degrades type IV collagen, the main structural component of basement membranes and gelatin. The main pathologic role of MMP-2 overexpression is to contribute to the development of cancer through the progression of metastasis and angiogenesis. A structure-based virtual screening was employed to find new inhibitors with possible selectivity for MMP-2. The inhibitory activities of 3 inhibitors (one was not a suitable drug-like hit) among 19 purchased compounds were approved by enzyme inhibition assay. 5 hits were non-zinc-binding inhibitors of MMP-2. The results demonstrated that a computer-aided drug design could be successfully applied for discovering new MMP-2 inhibitors. We found inhibitors with new scaffolds for the inhibition of MMP-2 with some selectivity features that could be used for future lead optimization processes. According to the docked pose and MD simulation, compound 13 was expected to interact with the S1' specificity loop of MMP-2 and had 2 π-π interactions and a stable hydrogen bond with the MMP-2 active site. The key feature of compound 13 could be used to guide the design of new non-zinc-binding inhibitors of MMP-2.

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“…Therefore, we use molecular docking simulation to explore the antiphotoaging structure–activity relationship for peptide with MMP-1 and MMP-9. Most inhibition with less selectivity precisely because active sites of the MMPs are over-conservative (52), while the structures of MMPs are analogical, and the dominating distinction rests in the S1’ pocket. MMP-1 could be inactivated by docking its S1’ and S3’ pockets.…”

Section: Discussionmentioning

confidence: 99%

Antiphotoaging effect of boiled abalone residual peptide ATPGDEG on UVB-induced keratinocyte HaCaT cells

Chen

Peng

Xiao

et al. 2019

Food & Nutrition Research

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IntroductionA previous study has shown that Ala–Thr–Pro–Gly–Asp–Glu–Gly (ATPGDEG) peptide identified from boiled abalone by-products has high antioxidant activities and antihypertensive effect.ObjectiveIn this study, we further investigated its antiphotoaging activities by ultraviolet B (UVB)-induced HaCaT cells.ResultUVB irradiation significantly increased the content of intercellular reactive oxygen species (ROS) and the production of matrix metalloproteinases (MMPs) in HaCaT cells and decreased its content of collagen. First, the generation of intercellular ROS was reduced by abalone peptide in UVB-induced HaCaT cells. And activities of MMP-1 and MMP-9 were reduced by abalone peptide in a dose-dependent manner. Furthermore, western blot analysis demonstrated that abalone peptide downregulated the expression of p38, c-Jun N-terminal kinases, and extracellular signal-regulated kinases via mitogen-activated protein kinases (MAPKs) and NF-κB signaling to protect type I pro collagen and DNA damage. Molecular docking simulation confirms that abalone peptide inhibited activities of MMP-1 and MMP-9 by docking their active site, among them N-terminal Ala, C-terminal Gly, and Pro at the third position of N-terminal made a great contribution.Conclusion and recommendationAbalone peptide could protect type I procollagen synthesis in UVB-irradiated HaCaT cells, and it is a potential peptide for the treatment of skin photoaging in the future.

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Synthesis and discovery of (I-3,II-3)-biacacetin as a novel non-zinc binding inhibitor of MMP-2 and MMP-9

Cited by 27 publications

References 12 publications

Seeking for Non-Zinc-Binding MMP-2 Inhibitors: Synthesis, Biological Evaluation and Molecular Modelling Studies

Seeking for Non-Zinc-Binding MMP-2 Inhibitors: Synthesis, Biological Evaluation and Molecular Modelling Studies

Identification of Non-Zinc Binding Inhibitors of MMP-2 Through Virtual Screening and Subsequent Rescoring

Antiphotoaging effect of boiled abalone residual peptide ATPGDEG on UVB-induced keratinocyte HaCaT cells

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