Abstract
Diabetes mellitus in rats is characterized by excessive activity of several matrix metalloproteinases (MMPs), notably collagenase(s) and gelatinase(s), in skin, gingiva, and other tissues. A number of tetracyclines (TCs), both antimicrobial compounds as well as chemically modified non-antimicrobial TC analogues (CMTs) are known to possess potent inhibitory activity against these enzymes. Three conventional antimicrobial TCs and six CMTs were used in this study. In vitro, doxycycline was shown to possess higher inhibitory capacity (i.e. lower IC 50 ) against diabetic rat skin collagenase than either minocycline or tetracycline HCl. Addition of excess zinc partially reversed the proteinase inhibition by TCs. In vivo, using rats made diabetic with streptozotocin (STZ), oral administration of various TCs led to decreased weight loss and substantial reductions in the activity of both skin collagenase and skin gelatinase (primarily MMP-9, 92 kDa) without affecting blood glucose. Using an in vitro spectrophotometric technique, the Zn positive2 reactivity of several CMTs was assessed and found to be positively related to the potency of these compounds as MMP inhibitors. One particular CMT (CMT-5, pyrazole analogue), which is neither antimicrobial nor capable of binding metal cations, did not inhibit the MMPs. TCs have potential utility in management of diabetic complications mediated by excessive activity of MMPs.
Keywords: matrix metalloprotienase activity, tetracycline analogues, streptozotocin STZ, matrix metalloproteinase, chemotheraputics, non antimicrobial CMTs, organomercurial agent, aminophenylmercuric acetate, zinc binding studies, pyrazole analogue, collagenase and gelatinase activity
Current Medicinal Chemistry
Title: Excessive Matrix Metalloproteinase Activity in Diabetes: Inhibition by Tetracycline Analogues with Zinc Reactivity
Volume: 8 Issue: 3
Author(s): Maria E. Ryan, Adil Usman, N. S. Ramamurthy, Lorne M. Golub and Robert A. Greenwald
Affiliation:
Keywords: matrix metalloprotienase activity, tetracycline analogues, streptozotocin STZ, matrix metalloproteinase, chemotheraputics, non antimicrobial CMTs, organomercurial agent, aminophenylmercuric acetate, zinc binding studies, pyrazole analogue, collagenase and gelatinase activity
Abstract: Diabetes mellitus in rats is characterized by excessive activity of several matrix metalloproteinases (MMPs), notably collagenase(s) and gelatinase(s), in skin, gingiva, and other tissues. A number of tetracyclines (TCs), both antimicrobial compounds as well as chemically modified non-antimicrobial TC analogues (CMTs) are known to possess potent inhibitory activity against these enzymes. Three conventional antimicrobial TCs and six CMTs were used in this study. In vitro, doxycycline was shown to possess higher inhibitory capacity (i.e. lower IC 50 ) against diabetic rat skin collagenase than either minocycline or tetracycline HCl. Addition of excess zinc partially reversed the proteinase inhibition by TCs. In vivo, using rats made diabetic with streptozotocin (STZ), oral administration of various TCs led to decreased weight loss and substantial reductions in the activity of both skin collagenase and skin gelatinase (primarily MMP-9, 92 kDa) without affecting blood glucose. Using an in vitro spectrophotometric technique, the Zn positive2 reactivity of several CMTs was assessed and found to be positively related to the potency of these compounds as MMP inhibitors. One particular CMT (CMT-5, pyrazole analogue), which is neither antimicrobial nor capable of binding metal cations, did not inhibit the MMPs. TCs have potential utility in management of diabetic complications mediated by excessive activity of MMPs.
Export Options
About this article
Cite this article as:
Ryan E. Maria, Usman Adil, Ramamurthy S. N., Golub M. Lorne and Greenwald A. Robert, Excessive Matrix Metalloproteinase Activity in Diabetes: Inhibition by Tetracycline Analogues with Zinc Reactivity, Current Medicinal Chemistry 2001; 8 (3) . https://dx.doi.org/10.2174/0929867013373598
DOI https://dx.doi.org/10.2174/0929867013373598 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
![Wayfinder Image](/images/wayfinder.jpg)
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Mechanisms of Neuroprotection by Polyphenols
Current Medicinal Chemistry - Central Nervous System Agents A Possible Placental Factor for Preeclampsia: sFlt-1
Current Medicinal Chemistry NRF2-Dependent Glutamate-L-Cysteine Ligase Catalytic Subunit Expression Mediates Insulin Protection Against Hyperglycemia-Induced Brain Endothelial Cell Apoptosis
Current Neurovascular Research Bronchopulmonary Dysplasia: An Imbalance of Inflammation
Current Respiratory Medicine Reviews Molecular Chaperone ORP150 in ER Stress–related Diseases
Current Pharmaceutical Design Intravitreal Inserts of Steroids to Treat Diabetic Macular Edema
Current Diabetes Reviews Mechanism of Action and Implication of Naphthoquinone as Potent Anti-trypanosomal Drugs
Current Topics in Medicinal Chemistry The Last Decade of Carbon Paste Electrodes in DNA Electrochemistry
Current Analytical Chemistry Antioxidative Properties of Flavonoids
Current Organic Chemistry Natural AMPK Activators: An Alternative Approach for the Treatment and Management of Metabolic Syndrome
Current Medicinal Chemistry Finerenone: A Novel Drug Discovery for the Treatment of Chronic Kidney Disease
Current Drug Discovery Technologies MicroRNAs: Newcomers into the ALS Picture
CNS & Neurological Disorders - Drug Targets Pancreatic Islet Transplantation in Type 1 Diabetes Mellitus: An Update on Recent Developments
Current Diabetes Reviews Medical Management of the Diabetic Patient with Coronary Artery Disease
Current Pharmaceutical Design Heme Oxygenase-1 and Iron in Liver Inflammation: A Complex Alliance
Current Drug Targets Organic Cation Transporters: Physiology, Toxicology and Special Focus on Ethidium as a Novel Substrate
Current Drug Metabolism Signaling Mechanisms Underlying Aβ Toxicity: Potential Therapeutic Targets for Alzheimers Disease
CNS & Neurological Disorders - Drug Targets Pharmacological Benefits of Active Components of Natural Products Against Traumatic Brain Injury - A Review
Current Pharmacogenomics and Personalized Medicine Recent Advances in the Development of MMPIs and APNIs Based on the Pyrrolidine Platforms
Mini-Reviews in Medicinal Chemistry Cardiac Applications for Human Pluripotent Stem Cells
Current Pharmaceutical Design