Glucocorticoids (GCs) have been used in the treatment of sepsis because of their potent anti-inflammatory effects. However, their clinical efficacy against sepsis remains controversial because of ...glucocorticoid receptor (GR) downregulation and side effects. Herein, we designed and synthesized 30 ocotillol derivatives and evaluated their anti-inflammatory activities. Ocotillol 24(R/S) differential isomers were stereoselective in their pharmacological action. Specifically, 24(S) derivatives had better anti-inflammatory activity than their corresponding 24(R) derivatives. Compound 20 most effectively inhibited NO release (85.97% reduction), and it exerted dose-dependent inhibitory effects on interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels. Mechanistic studies revealed that compound 20 reduces the degradation of GR mRNA and GR protein. Meanwhile, compound 20 inhibited the activation of nuclear factor-κB (NF-κB) signaling, thereby inhibiting the nuclear translocation of p65 and attenuating the inflammatory response. In vivo studies revealed that compound 20 attenuated hepatic, pulmonary, and renal pathology damage in mice with sepsis and suppressed the production of inflammatory mediators. These results indicated that compound 20 is a promising lead compound for designing and developing anti-sepsis drugs.
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•30 novel ocotillol derivatives were synthesized.•Compound 20 showed the best anti-inflammatory activity.•Compound 20 reduces the degradation of GR mRNA and GR protein.•Compound 20 inhibits the activation of the NF-κB signaling, attenuating the inflammatory response.•Compound 20 significantly attenuated hepatic, pulmonary and renal pathology damage in septic mice.
Acute lung injury (ALI) and inflammatory bowel disease (IBD) are common inflammatory illnesses that seriously affect people's health. Herein, a series of 4-hydroxylcoumarin (4-HC) derivatives were ...designed and synthesized. The inhibitory effects of these compounds on LPS-induced interleukin-6 (IL-6) release from J774A.1 cells were then screened via ELISA assay, compound B8 showed 3 times more active than the lead compound 4-HC. The most active compound B8 had the IC50 values of 4.57 μM and 6.51 μM for IL-6 release on mouse cells J774A.1 and human cells THP-1, respectively. Furthermore, we also found that B8 could act on the MAPK pathway. Based on the target prediction results of computer virtual docking, kinase inhibitory assay was carried out, and it revealed that targeting IRAK1 was a key mechanism for B8 to exert anti-inflammatory activity. Moreover, B8 exerted a good therapeutic effect on the dextran sulfate sodium (DSS)-induced colitis model and liposaccharide (LPS)-induced ALI mouse models. The acute toxicity experiments indicated that high-dose B8 caused no adverse reactions in mice, confirming its safety in vivo. Additionally, the preliminary pharmacokinetic (PK) parameters of B8 in SD rats were also examined, revealing a bioavailability (F) of 28.72 %. In conclusion, B8 is a potential candidate of drug for the treatment of ALI and colitis.
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•A series of 4-hydroxycoumarin derivatives were designed and synthesized.•B8 inhibited the release of IL-6 and its mRNA expression on J774A.1/THP-1 cells.•B8 could inhibit the MAPK pathway and target on IRAK1.•B8 could significantly ameliorate LPS-induced ALI and DSS-induced colitis.
A series of previously synthesized 5-benzyliden-2-(5-methylthiazole-2-ylimino)thiazoli- din-4-one were evaluated for their anti-inflammatory activity on the basis of PASS predictive outcomes. The ...predictive compounds were found to demonstrate moderate to good anti-inflammatory activity, and some of them displayed better activity than indomethacin used as the reference drug. Structure-activity relationships revealed that the activity of compounds depends not only on the nature of the substituent but also on its position in the benzene ring. The most active compounds were selected to investigate their possible mechanism of action. COX and LOX activity were determined and found that the title compounds were active only to COX-1 enzymes with an inhibitory effect superior to the reference drug naproxen. As for LOX inhibitory activity, the derivatives failed to show remarkable LOX inhibition. Therefore, COX-1 has been identified as the main molecular target for the anti-inflammatory activity of our compounds. The docking study against COX-1 active site revealed that the residue Arg 120 was found to be responsible for activity. In summary, the 5-thiazol-based thiazolidinone derivatives have been identified as a novel class of selective COX-1 inhibitors.
Objective
To provide a systematic review of the literature regarding the efficacy of anti‐inflammatory drugs in three major mental disorders major depressive disorder (MDD), schizophrenia and bipolar ...disorders.
Method
Four databases were explored, without any year or language restrictions. The baseline search paradigm was limited to open‐labelled clinical and randomized controlled trials (RCTs).
Results
Four major classes of anti‐inflammatory drugs were identified, namely polyunsaturated fatty acids (PUFAs), cyclooxygenase (COX) inhibitors, anti‐TNFalpha and minocycline. Effectiveness and benefit/risk ratio of each class in MDD, bipolar disorders and schizophrenia was detailed when data were available. Several meta‐analyses indicated effectiveness of PUFAs in MDD with a good tolerance profile. One meta‐analysis indicated that COX‐2 specific inhibitors showed effectiveness in schizophrenia. Anti‐TNFalpha showed important effectiveness in resistant MDD with blood inflammatory abnormalities. Minocycline showed effectiveness in schizophrenia.
Conclusion
Polyunsaturated fatty acids seem to have the best benefit/risk ratio profile but proved their effectiveness only in MDD. A number of anti‐inflammatory drugs are available as adjunct treatment for treatment‐resistant patients with MDD, schizophrenia and bipolar disorder. If used with caution regarding their possible side‐effects, they may be reasonable therapeutic alternatives for resistant symptomatology.
Inflammation is a natural protective mechanism that occurs when the body's tissue homeostatic mechanisms are disrupted by biotic, physical, or chemical agents. The immune response generates ...pro-inflammatory mediators, but excessive output, such as chronic inflammation, contributes to many persistent diseases. Some phenolic compounds work in tandem with nonsteroidal anti-inflammatory drugs (NSAIDs) to inhibit pro-inflammatory mediators' activity or gene expression, including cyclooxygenase (COX). Various phenolic compounds can also act on transcription factors, such as nuclear factor-κB (NF-κB) or nuclear factor-erythroid factor 2-related factor 2 (Nrf-2), to up-or downregulate elements within the antioxidant response pathways. Phenolic compounds can inhibit enzymes associated with the development of human diseases and have been used to treat various common human ailments, including hypertension, metabolic problems, incendiary infections, and neurodegenerative diseases. The inhibition of the angiotensin-converting enzyme (ACE) by phenolic compounds has been used to treat hypertension. The inhibition of carbohydrate hydrolyzing enzyme represents a type 2 diabetes mellitus therapy, and cholinesterase inhibition has been applied to treat Alzheimer's disease (AD). Phenolic compounds have also demonstrated anti-inflammatory properties to treat skin diseases, rheumatoid arthritis, and inflammatory bowel disease. Plant extracts and phenolic compounds exert protective effects against oxidative stress and inflammation caused by airborne particulate matter, in addition to a range of anti-inflammatory, anticancer, anti-aging, antibacterial, and antiviral activities. Dietary polyphenols have been used to prevent and treat allergy-related diseases. The chemical and biological contributions of phenolic compounds to cardiovascular disease have also been described. This review summarizes the recent progress delineating the multifunctional roles of phenolic compounds, including their anti-inflammatory properties and the molecular pathways through which they exert anti-inflammatory effects on metabolic disorders. This study also discusses current issues and potential prospects for the therapeutic application of phenolic compounds to various human diseases.
Due to its important biological and pharmacological properties, in the field of medicinal chemistry and drug discovery, the N-acylhydrazone motif has shown to be extremely adaptable and promising. ...This scaffold has become a crucial component in the synthesis of numerous bioactive agents.
-Acylhydrazones are also interesting biological and synthetic tools due to their easy and straightforward synthesis. The current review provides a summary of the analgesic and anti-inflammatory activities of
-acylhydrazone derivatives over the past ten years. A brief discussion of structure-activity relationships is also provided which may guide researchers in medicinal chemistry to develop derivatives based on
-acylhydrazone scaffold as potent anti-inflammatory candidates.
Copper-based compounds are promising entities for target-specific next-generation anticancer and NSAIDS therapeutics. In lieu of this, benzimidazole scaffold plays an important role, because of their ...wide variety of potential functionalizations and coordination modes. Herein, we report three copper complexes 1-3 with benzimidazole-derived scaffolds, a biocompatible molecule, and secondary ligands viz, 1-10-phenanthroline and 2,2'-bipyridyl. All the copper complexes have been designed, synthesized and adequately characterized using various spectroscopic techniques. In-vitro, human serum albumin (HSA) binding was also carried out using fluorescence technique and in-silico molecular modeling studies, which exhibited significant binding affinities of the complexes with HSA. Furthermore, copper complexes 1-3 were tested for biological studies, i.e., anticancer as well as NSAIDS. In vitro cytotoxicity results were carried out on cultured MCF-7 cell lines. To get the insight over the mechanism of action, GSH depletion and change in lipid peroxidation were tested and thus confirmed the role of ROS generation, responsible for the cytotoxicity of the complexes 1-3. Moreover, the copper complexes 1-3 were tested for potential to act as NSAIDS on albino rats and mice in animal studies in-vivo. Additionally, we also predicted the mechanism of action of the copper complexes 1-3 using molecular modeling studies with COX-2 inhibitor.
Anti-Inflammatory Drugs as Anticancer Agents Zappavigna, Silvia; Cossu, Alessia Maria; Grimaldi, Anna ...
International journal of molecular sciences,
04/2020, Letnik:
21, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Inflammation is strictly associated with cancer and plays a key role in tumor development and progression. Several epidemiological studies have demonstrated that inflammation can predispose to ...tumors, therefore targeting inflammation and the molecules involved in the inflammatory process could represent a good strategy for cancer prevention and therapy. In the past, several clinical studies have demonstrated that many anti-inflammatory agents, including non-steroidal anti-inflammatory drugs (NSAIDs), are able to interfere with the tumor microenvironment by reducing cell migration and increasing apoptosis and chemo-sensitivity. This review focuses on the link between inflammation and cancer by describing the anti-inflammatory agents used in cancer therapy, and their mechanisms of action, emphasizing the use of novel anti-inflammatory agents with significant anticancer activity.
Though inflammatory response is beneficial to body damage repair, if it is out of control, it can produce adverse effects on the body. Although purely western anti-inflammatory drugs, orthodox ...medicines, can control inflammation occurrence and development, it is not enough. The clinical efficacy of anti-inflammation therapies is unsatisfactory, thus the search for new anti-inflammation continues. Chinese Material Medica (CMM) remains a promising source of new therapeutic agents. CMM and herbal formulae from Traditional Chinese Medicine (TCM), unorthodox medicines, play an improtant anti-inflammatory role in multi-targets, multi-levels, and multi-ways in treating inflammation diseases in a long history in China, based on their multi-active ingredient characteristics. Due to these reasons, recently, CMM has been commercialized as an anti-inflammation agent which has become increasingly popular in the world health drug markets. Major research contributions in ethnopharmacology have generated vast amount of data associated with CMM in anti-inflammtion aspect. Therefore, a systematic introduction of CMM anti-inflammatory research progress is of great importance and necessity.
This paper strives to describe the progress of CMM in the treatment of inflammatory diseases from different aspects, and provide the essential theoretical support and scientific evidence for the further development and utilization of CMM resources as a potential anti-inflammation drug through a variety of databases.
Literature survey was performed via electronic search (SciFinder®, Pubmed®, Google Scholar and Web of Science) on papers and patents and by systematic research in ethnopharmacological literature at various university libraries.
This review mainly introduced the current research on the anti-inflammatory active ingredient, anti-inflammatory effects of CMM, their mechanism, anti-inflammatory drug development of CMM, and toxicological information.
CMM is used clinically to treat inflammation symptoms in TCM, and its effect is mediated by multiple targets through multiple active ingredients. Although scholars around the world have made studies on the anti-inflammatory studies of CMM from different pathways and aspects and have made substantial progress, further studies are warranted to delineate the inflammation actions in more cogency models, establish the toxicological profiles and quality standards, assess the potentials of CMM in clinical applications, and make more convenient preparations easy to administrate for patients. Development of the clinically anti-inflammatory drugs are also warranted.
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A new series of pyrrolopyridines and pyrrolopyridopyrimidines have been synthesized from aminocyanopyrroles. The synthesized compounds have been characterized by FTIR, ¹H-NMR and mass spectroscopy. ...The final compounds have been screened for in vitro pro-inflammatory cytokine inhibitory and in vivo anti-inflammatory activity. The biological results revealed that among all tested compounds some fused pyrroles, namely the pyrrolopyridines
and
, show promising activity. A docking study of the active synthesized molecules confirmed the biological results and revealed a new binding pose in the COX-2 binding site.
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