Thiophene-Based Compounds with Potential Anti-Inflammatory Activity

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.

Download Full-text

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

Current Medicinal Chemistry ◽

10.2174/0929867328666210910125229 ◽

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.

Download Full-text

Anti-Inflammatory Effect of 1,3,5,7-Tetrahydroxy-8-isoprenylxanthone Isolated from Twigs ofGarcinia esculentaon Stimulated Macrophage

Mediators of Inflammation ◽

10.1155/2015/350564 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Dan-Dan Zhang ◽

Hong Zhang ◽

Yuan-zhi Lao ◽

Rong Wu ◽

Jin-wen Xu ◽

...

Keyword(s):

Nitric Oxide ◽

Inflammatory Diseases ◽

Inflammatory Activity ◽

Drug Candidates ◽

P38mapk Signaling ◽

Cox 2 ◽

Anti Inflammatory ◽

Oxide Synthase ◽

Inducible Nitric Oxide ◽

Inflammatory Effect

GarciniaLinn. plants having rich natural xanthones and benzophenones with anti-inflammatory activity attracted a great deal of attention to discover and develop them as potential drug candidates. Through screening targeting nitric oxide accumulation in stimulated macrophage, we found that 1,3,5,7-tetrahydroxy-8-isoprenylxanthone (TIE) had potential anti-inflammatory effect. To understand how TIE elicits its anti-inflammatory activity, we uncovered that it significantly inhibits the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS/IFNγ-stimulated RAW264.7 cells. In further study, we showed that TIE reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), two key molecules responsible for the production of NO and PGE2 during inflammation progress. Additionally, TIE also suppressed the expression of inflammatory cytokines IL-6, IL-12, and TNF-α. TIE-led suppression in iNOS, COX-2, and cytokines production were probably the consequence of TIE’s capability to block ERK and p38MAPK signaling pathway. Moreover, TIE blocked activation of nuclear factor-kappa B (NF-κB) as well as NF-κB regulation of miR155 expression. Our study suggests that TIE may represent as a potential therapeutic agent for the treatment of inflammatory diseases.

Download Full-text

Effects of non-steroidal anti-inflammatory drugs and other eicosanoid pathway modifiers on antiviral and allergic responses. EAACI task force on eicosanoids consensus report in times of COVID-19

10.22541/au.163790432.20160380/v1 ◽

2021 ◽

Author(s):

Milena Sokolowska ◽

G Enrico Rovati ◽

Zuzana Diamant ◽

Eva Untersmayr ◽

Jürgen Schwarze ◽

...

Keyword(s):

Viral Infections ◽

Respiratory Infections ◽

Task Force ◽

Inflammatory Diseases ◽

Prostaglandin D2 ◽

Asthma Exacerbations ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Consensus Report

Non-steroidal anti-inflammatory drugs (NSAIDs) and other eicosanoid pathway modifiers are among the most ubiquitously used medications in the general population. Their broad anti-inflammatory, antipyretic and analgesic effects are applied against symptoms of respiratory infections, including SARS-CoV-2, as well as in other acute and chronic inflammatory diseases that often coexist with allergy and asthma. However, the current pandemic of COVID-19 also revealed the gaps in our understanding of their mechanism of action, selectivity and interactions not only during viral infections and inflammation, but also in asthma exacerbations, uncontrolled allergic inflammation, and NSAIDs-exacerbated respiratory disease (NERD). In this context, the consensus report summarises currently available knowledge, novel discoveries and controversies regarding the use of NSAIDs in COVID-19, and the role of NSAIDs in asthma and viral asthma exacerbations. We also describe here novel mechanisms of action of leukotriene receptor antagonists (LTRAs), outline how to predict responses to LTRA therapy and discuss a potential role of LTRA therapy in COVID-19 treatment. Moreover, we discuss interactions of novel T2 biologicals and other eicosanoid pathway modifiers on the horizon, such as prostaglandin D2 antagonists and cannabinoids, with eicosanoid pathways, in context of viral infections and exacerbations of asthma and allergic diseases. Finally, we identify and summarise the major knowledge gaps and unmet needs in current eicosanoid research.

Download Full-text

Medicinal Plants of the Australian Aboriginal Dharawal People Exhibiting Anti-Inflammatory Activity

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/2935403 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 7

Author(s):

Most A. Akhtar ◽

Ritesh Raju ◽

Karren D. Beattie ◽

Frances Bodkin ◽

Gerald Münch

Keyword(s):

Nitric Oxide ◽

Aboriginal People ◽

Inflammatory Diseases ◽

Autism Spectrum ◽

Inflammatory Activity ◽

Inflammatory Conditions ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Necrosis Factor

Chronic inflammation contributes to multiple ageing-related musculoskeletal and neurodegenerative diseases, cardiovascular diseases, asthma, rheumatoid arthritis, and inflammatory bowel disease. More recently, chronic neuroinflammation has been attributed to Parkinson’s and Alzheimer’s disease and autism-spectrum and obsessive-compulsive disorders. To date, pharmacotherapy of inflammatory conditions is based mainly on nonsteroidal anti-inflammatory drugs which in contrast to cytokine-suppressive anti-inflammatory drugs do not influence the production of cytokines such as tumour necrosis factor-α or nitric oxide. However, their prolonged use can cause gastrointestinal toxicity and promote adverse events such as high blood pressure, congestive heart failure, and thrombosis. Hence, there is a critical need to develop novel and safer nonsteroidal anti-inflammatory drugs possessing alternate mechanism of action. In this study, plants used by the Dharawal Aboriginal people in Australia for the treatment of inflammatory conditions, for example, asthma, arthritis, rheumatism, fever, oedema, eye inflammation, and inflammation of bladder and related inflammatory diseases, were evaluated for their anti-inflammatory activity in vitro. Ethanolic extracts from 17 Eucalyptus spp. (Myrtaceae) were assessed for their capacity to inhibit nitric oxide and tumor necrosis factor-α production in RAW 264.7 macrophages. Eucalyptus benthamii showed the most potent nitric oxide inhibitory effect (IC50 5.57±1.4 µg/mL), whilst E. bosistoana, E. botryoides, E. saligna, E. smithii, E. umbra, and E. viminalis exhibited nitric oxide inhibition values between 7.58 and 19.77 µg/mL.

Download Full-text

Synthesis and Biological Evaluation of Andrographolide Derivatives as Anti-inflammatory Agent

Current Pharmaceutical Design ◽

10.2174/1381612824666180724130014 ◽

2018 ◽

Vol 24 (30) ◽

pp. 3529-3533 ◽

Cited By ~ 6

Author(s):

Zeyu Zhu ◽

Haibing Duan ◽

Mei Jing ◽

Lipeng Xu ◽

Pei Yu

Keyword(s):

Bacterial Infections ◽

Inflammatory Diseases ◽

Cell Activity ◽

Biological Evaluation ◽

Inflammatory Activity ◽

Special Effects ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

New Compounds ◽

Synthesis And Biological Evaluation

Background: Andrographolide (Andro) is a main active ingredient of the natural plant Andrographis paniculata, which has special effects on bacterial infections and inflammatory diseases. Objective: We previously synthesized Andrographolide derivatives AL-1 and investigated its anti-inflammatory activity. For further research, we decided to modify the structure of AL-1 and expected to have better antiinflammatory activity. Methods: By conjugating with anti-inflammatory and anti-bacterial group, we designed and synthesized the andrographolide derivative AL-2, AL-3 and AL-4. The anti-inflammatory activity of AL-2, AL-3 and AL-4 was also evaluated by detecting cell activity and Nitric Oxide (NO) release. <p> Results: The new compounds AL-2, AL-3 and AL-4 increased cell viability in lipopolysaccharide (LPS)-induced RAW 264.7 cell, which could have a certain anti-inflammatory activity, and inhibited the release of NO in cells to reduce the inflammatory response of cells. Conclusion: The new compounds AL-2, AL-3 and AL-4 may be candidates of anti-inflammatory drugs in the future.

Download Full-text

The effect of inflammatory response modulator agents on gingivitis and periodontitis

RGO - Revista Gaúcha de Odontologia ◽

10.1590/1981-8637201600030000112165 ◽

2016 ◽

Vol 64 (3) ◽

pp. 312-319

Author(s):

Juliano CAVAGNI ◽

Francisco Wilker Mustafa Gomes MUNIZ ◽

Cassiano Kuchenbecker RÖSING

Keyword(s):

Host Response ◽

Animal Studies ◽

Inflammatory Diseases ◽

Periodontal Diseases ◽

Therapeutic Procedures ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Microbial Challenge

ABSTRACT Periodontal diseases are infecto-inflammatory diseases. Literature, has tried to elucidate the infections component of gingivitis and periodontitis, for several years. In recent years, much has been discussed about the role of the host response modulators to periodontal therapeutic procedures. The aim of the present literature review was to evaluate the effect of host response modulating agents (anti-inflammatories) on the pathogenesis of gingivitis and periodontitis. A search in the main databases was performed and human and animal studies were selected. The majority of studies was performed in humans and non-steroidal anti-inflammatory drugs in different dosages were used. The results have shown a potential benefit of the non-steroidal anti-inflammatory drugs concerning the microbial challenge. However, this benefit seems not to occur in the long term, thus not supporting it as a periodontal therapeutic approach. Few studies evaluated the effect of steroidal anti-inflammatory drugs on the pathogenesis of periodontal diseases. Moreover, the results in humans and animals are controversial, pointing to a possible deleterious effect of steroidal anti-inflammatory drugs on periodontal structures.

Download Full-text

Heparin and proteoglycans as anti-inflammatory drugs

Hämostaseologie ◽

10.1055/s-0038-1656639 ◽

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.

Download Full-text