Sulphonamides as Anti-Inflammatory Agents: Old Drugs for New Therapeutic Strategies in Neutrophilic Inflammation?

1995 ◽  
Vol 88 (3) ◽  
pp. 331-336 ◽  
Author(s):  
Luciano Ottonello ◽  
Patrizia Dapino ◽  
Maria C. Scirocco ◽  
Alessandro Balbi ◽  
Maurizio Bevilacqua ◽  
...  
Keyword(s):  
Hypochlorous Acid ◽  
Tissue Injury ◽  
Inflammatory Diseases ◽  
Specific Inhibitor ◽  
Therapeutic Strategies ◽  
Dependent Manner ◽  
Neutrophilic Inflammation ◽  
Starting Point ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

1. It is well known that neutrophils act as mediators of tissue injury in a variety of inflammatory diseases. Their histotoxic activity is presently thought to involve proteinases and oxidants, primarily hypochlorous acid (HOCl). This oxidant is also capable of inactivating the specific inhibitor of neutrophil elastase (α1-antitrypsin), thereby favouring digestion of the connective matrix. 2. In the present work, we found that sulphanilamide and some sulphanilamide-related anti-inflammatory drugs such as dapsone, nimesulide and sulphapyridine reduce the availability of HOCl in the extracellular microenvironment of activated neutrophils and prevent the inactivation of α1-antitrypsin by these cells in a dose-dependent manner. The ability of each drug to prevent α1-antitrypsin from inactivation by neutrophils correlates significantly with its capacity to reduce the recovery of HOCl from neutrophils. Five other non-steroidal anti-inflammatory drugs were completely ineffective. 3. Therefore, sulphanilamide-related drugs, i.e. dapsone, nimesulide and sulphapyridine, have the potential to reduce the bioavailability of neutrophil-derived HOCl and, in turn, to favour the α1-antitrypsin-dependent control of neutrophil elastolytic activity. These drugs appear as a well-defined group of agents which are particularly prone to attenuate neutrophil histotoxicity. They can also be viewed as a previously unrecognized starting point for the development of new compounds in order to plan rational therapeutic strategies for controlling tissue injury during neutrophilic inflammation.

Heparin and proteoglycans as anti-inflammatory drugs

1996 ◽  
Vol 16 (01) ◽  
pp. 56-59
Author(s):  
D. J. Tyrrell ◽  
C. P. Page
Keyword(s):  
Inflammatory Diseases ◽  
Therapeutic Applications ◽  
Wide Range ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

SummaryEvidence continues to accumulate that the pleiotropic nature of heparin (beyond its anticoagulant potency) includes anti-inflammatory activities at a number of levels. It is clear that drugs exploiting these anti-inflammatory activities of heparin may offer exciting new therapeutic applications to the treatment of a wide range of inflammatory diseases.

scholarly journals Thiophene-Based Compounds with Potential Anti-Inflammatory Activity

2021 ◽  
Vol 14 (7) ◽  
pp. 692
Author(s):  
Ryldene Marques Duarte da Cruz ◽  
Francisco Jaime Bezerra Mendonça-Junior ◽  
Natália Barbosa de Mélo ◽  
Luciana Scotti ◽  
Rodrigo Santos Aquino de Araújo ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Structural Characteristics ◽  
Tiaprofenic Acid ◽  
Inflammatory Activity ◽  
Drug Candidates ◽  
Biological Target ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Privileged Structures

Rheumatoid arthritis, arthrosis and gout, among other chronic inflammatory diseases are public health problems and represent major therapeutic challenges. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed clinical treatments, despite their severe side effects and their exclusive action in improving symptoms, without effectively promoting the cure. However, recent advances in the fields of pharmacology, medicinal chemistry, and chemoinformatics have provided valuable information and opportunities for development of new anti-inflammatory drug candidates. For drug design and discovery, thiophene derivatives are privileged structures. Thiophene-based compounds, like the commercial drugs Tinoridine and Tiaprofenic acid, are known for their anti-inflammatory properties. The present review provides an update on the role of thiophene-based derivatives in inflammation. Studies on mechanisms of action, interactions with receptors (especially against cyclooxygenase (COX) and lipoxygenase (LOX)), and structure-activity relationships are also presented and discussed. The results demonstrate the importance of thiophene-based compounds as privileged structures for the design and discovery of novel anti-inflammatory agents. The studies reveal important structural characteristics. The presence of carboxylic acids, esters, amines, and amides, as well as methyl and methoxy groups, has been frequently described, and highlights the importance of these groups for anti-inflammatory activity and biological target recognition, especially for inhibition of COX and LOX enzymes.

scholarly journals Accumulation of Non-steroidal Anti-inflammatory Drugs by Gingival Fibroblasts

2006 ◽  
Vol 85 (5) ◽  
pp. 452-456 ◽  
Author(s):  
M.M. Zavarella ◽  
O. Gbemi ◽  
J.D. Walters
Keyword(s):  
Steady State ◽  
Connective Tissue ◽  
Inflammatory Mediator ◽  
Dependent Manner ◽  
Gingival Fibroblasts ◽  
Temperature Dependent ◽  
Tnf Α ◽  
Steady State Levels ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Non-steroidal anti-inflammatory drugs (NSAIDs) are used to manage pain and inflammatory disorders. We hypothesized that gingival fibroblasts actively accumulate NSAIDs and enhance their levels in gingival connective tissue. Using fluorescence to monitor NSAID transport, we demonstrated that cultured gingival fibroblasts transport naproxen in a saturable, temperature-dependent manner with a Km of 127 μg/mL and a Vmax of 1.42 ng/min/μg protein. At steady state, the intracellular/extracellular concentration ratio was 1.9 for naproxen and 7.2 for ibuprofen. Naproxen transport was most efficient at neutral pH and was significantly enhanced upon cell treatment with TNF-α. In humans, systemically administered naproxen attained steady-state levels of 61.9 μg/mL in blood and 9.4 μg/g in healthy gingival connective tissue, while ibuprofen attained levels of 2.3 μg/mL and 1.5 μg/g, respectively. Thus, gingival fibroblasts possess transporters for NSAIDs that are up-regulated by an inflammatory mediator, but there is no evidence that they contribute to elevated NSAID levels in healthy gingiva.

The role of celecoxib as a potential inhibitor in the treatment of inflammatory diseases - a review

2021 ◽  
Vol 28 ◽  
Author(s):  
Josiane Viana Cruz ◽  
Joaquín María Campos Rosa ◽  
Njogu Mark Kimani ◽  
Silvana Giuliatti ◽  
Cleydson Breno Rodrigues dos Santos
Keyword(s):  
Side Effects ◽  
Inflammatory Diseases ◽  
Structural Basis ◽  
Potential Inhibitor ◽  
Cyclooxygenase 1 ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors

: This article presents a simplified view of celecoxib as a potential inhibitor in the treatment of inflammatory diseases. The enzyme cyclooxygenase (COX) has, predominantly, two isoforms called cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). The former plays a constitutive role that is related to homeostatic effects in renal and platelets, while the latter is mainly responsible for induction of inflammatory effects. Since COX-2 plays an important role in the pathogenesis of inflammatory diseases, it has been signaled as a target for the planning of anti-inflammatory intermediates. Many inhibitors developed and planned for COX-2 inhibition have presented side effects to humans, mainly in the gastrointestinal and/or cardiovascular tract. Therefore, it is necessary to design new potential COX-2 inhibitors, which are relatively safe and without side effects. To this end, of the generation of non-steroidal anti-inflammatory drugs from “coxibs”, celecoxib is the only potent selective COX-2 inhibitor that is still commercially available. Thus, the compound celecoxib became a commercial prototype inhibitor for the development of anti-inflammatory agents for COX-2 enzyme. In this review, we provide highlights where such inhibition should provide a structural basis for the design of promising new non-steroidal anti-inflammatory drugs (NSAIDs) which act as COX-2 inhibitors with lesser side effects on the human body.

Toxic effects of cell-free hemoglobin on the microvascular endothelium: implications for pulmonary and non-pulmonary organ dysfunction

2021 ◽  
Author(s):  
Jamie E Meegan ◽  
Julie A. Bastarache ◽  
Lorraine B. Ware
Keyword(s):  
Organ Dysfunction ◽  
Tissue Injury ◽  
Inflammatory Diseases ◽  
Severity Of Illness ◽  
Therapeutic Strategies ◽  
Free Hemoglobin ◽  
Microvascular Endothelium ◽  
Endothelial Inflammation ◽  
Signaling Mechanisms ◽  
Novel Therapeutic Strategies

Levels of circulating cell-free hemoglobin are elevated during hemolytic and inflammatory diseases and contribute to organ dysfunction and severity of illness. Though several studies have investigated the contribution of hemoglobin to tissue injury, the precise signaling mechanisms of hemoglobin-mediated endothelial dysfunction in the lung and other organs are not yet completely understood. The purpose of this review is to highlight the knowledge gained thus far and the need for further investigation regarding hemoglobin-mediated endothelial inflammation and injury in order to develop novel therapeutic strategies targeting the damaging effects of cell-free hemoglobin.

scholarly journals A concise review on advances in development of small molecule anti-inflammatory therapeutics emphasising AMPK: An emerging target

2016 ◽  
Vol 29 (4) ◽  
pp. 562-571 ◽  
Author(s):  
Chethan Gejjalagere Honnappa ◽  
Unnikrishnan Mazhuvancherry Kesavan
Keyword(s):  
Drug Targets ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Cyclooxygenase Inhibitors ◽  
Evolutionarily Conserved ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Acid Pathway ◽  
Clinical Trial Results ◽  
Amp Activated Protein Kinase

Inflammatory diseases are complex, multi-factorial outcomes of evolutionarily conserved tissue repair processes. For decades, non-steroidal anti-inflammatory drugs and cyclooxygenase inhibitors, the primary drugs of choice for the management of inflammatory diseases, addressed individual targets in the arachidonic acid pathway. Unsatisfactory safety and efficacy profiles of the above have necessitated the development of multi-target agents to treat complex inflammatory diseases. Current anti-inflammatory therapies still fall short of clinical needs and the clinical trial results of multi-target therapeutics are anticipated. Additionally, new drug targets are emerging with improved understanding of molecular mechanisms controlling the pathophysiology of inflammation. This review presents an outline of small molecules and drug targets in anti-inflammatory therapeutics with a summary of a newly identified target AMP-activated protein kinase, which constitutes a novel therapeutic pathway in inflammatory pathology.

Anti-Inflammatory Drugs and Herbs with Special Emphasis on Herbal Medicines for Countering Inflammatory Diseases and Disorders - A Review

2018 ◽  
Vol 12 (1) ◽  
pp. 39-58 ◽  
Author(s):  
Mohd. I. Yatoo ◽  
Arumugam Gopalakrishnan ◽  
Archana Saxena ◽  
Oveas R. Parray ◽  
Noore A. Tufani ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Herbal Medicines ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

STUDY OF SPECIFIC PHARMACOLOGICAL ACTIVITY OF SODIUM SALT (4-О-Β-GLUCOPYRANOSYLOXY)-BENZOIC ACID

2016 ◽  
Vol 78 (6-8) ◽  
Author(s):  
Smirnov Ivan ◽  
Murashko Tatyana ◽  
Ivanov Alex ◽  
Bondarev Alex ◽  
Udut Vladimir
Keyword(s):  
Benzoic Acid ◽  
Analgesic Activity ◽  
Sodium Salt ◽  
Analgesic Effect ◽  
Inflammatory Diseases ◽  
Peptic Ulcers ◽  
Chronic Inflammatory Diseases ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Chronic inflammatory diseases of various genesis are prevalent today. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain and inflammation, but their long-term use is associated with complications in the gastrointestinal tract, including peptic ulcers. We synthesized a molecule of sodium salt (4-О-β-glucopyranosyloxy)-benzoic acid. This substance has diuretic and anti-inflammatory activities. It should be noted that most of NSAIDs has analgesic effect. In this connection, the aim of this study was to evaluate the analgesic activity of sodium salt (4-О-β-glucopyranosyloxy)-benzoic acid. We studied analgesic effect in the test “acetic writhing”. Sodium salt (4-О-β-glucopyranosyloxy)-benzoic acid significantly reduces the number of writhing by 14 units during the experiment, as an alternative criterion percent of animals with analgesia was 42.6%. Thus, in the test "acetic writhing" revealed the presence of the analgesic activity have developed drug average severity. 

scholarly journals ANTI-INFLAMMATORY ACTIVITY OF TINOCRISPOSIDE BY INHIBITING NITRIC OXIDE PRODUCTION IN LIPOPOLYSACCHARIDES-STIMULATED RAW 264.7 CELLS

2018 ◽  
Vol 11 (4) ◽  
pp. 149 ◽  
Author(s):  
Adek Zamrud Adnan ◽  
Muhammad Taher ◽  
Tika Afriani ◽  
Annisa Fauzana ◽  
Dewi Imelda Roesma ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Diseases ◽  
Positive Control ◽  
Inflammatory Activity ◽  
Raw 264.7 Cells ◽  
No Production ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Anti Inflammatory

 Objective: The aim of this study was to investigate in vitro anti-inflammatory activity of tinocrisposide using lipopolysaccharides (LPS)-stimulated RAW 264.7 macrophage cells. Tinocrisposide is a furano diterpene glycoside that was isolated in our previous study from Tinospora crispa.Methods: Anti-inflammatory effect was quantified spectrometrically using Griess method by measuring nitric oxide (NO) production after the addition of Griess reagent.Results: The sample concentrations of 1, 5, 25, 50, and 100 μM and 100 μM of dexamethasone (positive control) have been tested against the LPS-stimulated RAW 264.7 cells, and the results showed NO level production of 39.23, 34.00, 28.9, 20.25, 16.3, and 13.68 μM, respectively, and the inhibition level of 22.67, 33.00, 43.03, 60.10, 68.00, and 73%, respectively.Conclusions: From the study, it could be concluded that tinocrisposide was able to inhibit the formation of NO in the LPS-stimulated RAW 264.7 cells in concentration activity-dependent manner, with half-maximal inhibition concentration 46.92 μM. It can be developed as anti-inflammatory candidate drug because NO is a reactive nitrogen species which is produced by NO synthase. The production of NO has been established as a mediator in inflammatory diseases.

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