Synthesis, Anti-inflammatory Activity and Docking Studies of Some Newer 1,3-Thiazolidine-2,4-dione Derivatives as Dual Inhibitors of PDE4 and PDE7

2019 ◽  
Vol 15 (3) ◽  
pp. 225-234 ◽  
Author(s):  
Himanshu Sharma ◽  
Viney Lather ◽  
Ajmer Singh Grewal ◽  
Deepti Pandita
Keyword(s):  
In Silico ◽  
Cell Function ◽  
Inflammatory Diseases ◽  
Research Work ◽  
Docking Studies ◽  
Inflammatory Activity ◽  
In Silico Docking ◽  
Dual Inhibitors ◽  
Anti Inflammatory

<P>Background: Phosphodiesterase 4 (PDE4) and phosphodiesterase 7 (PDE7), PDE superfamily members, increase inflammatory processes in immunomodulatory as well as pro-inflammatory cells via breakdown of cyclic adenosine monophosphate. Dual inhibitors of PDE4 and PDE7 are a novel class of drug candidates which can regulate pro-inflammatory as well as T-cell function and can be particularly advantageous in the treatment of a wide-ranging disorders associated with the immune system as well as inflammatory diseases with fewer unwanted adverse effects. Objective: The current research work was planned to design and synthesize some newer substituted 1,3- thiazolidine-2,4-dione derivatives as dual inhibitors of PDE4 and PDE7 followed by evaluation of their anti-inflammatory activity and in silico docking studies. Methods: A new series of substituted 1,3-thiazolidine-2,4-dione derivatives was synthesized followed by evaluation of their anti-inflammatory activity in animal models. In silico docking studies were performed for the evaluation of the binding pattern of synthesized derivatives in the binding site of both PDE4 and PDE7 proteins. Results: Amongst the newly synthesized derivatives, compounds 5 and 12 showed higher antiinflammatory activity in the animal model. The results of in vivo animal studies were found to be in concordance with the results of molecular docking studies. Conclusion: These newly synthesized derivatives can act as the lead molecules for the design of safe and therapeutically effective agents for various inflammatory diseases acting via inhibition of both PDE4 and PDE7.</P>

Trigonella foenum-graecum Seeds Oil Attenuated Inflammation and Angiogenesis In Vivo through Down-Regulation of TNF-α

2020 ◽  
Vol 20 ◽  
Author(s):  
Muhammad Asif ◽  
Hafiz Muhammad Yousaf ◽  
Mohammed Saleem ◽  
Malik Saadullah ◽  
Tahir Ali Chohan ◽  
...  
Keyword(s):  
In Silico ◽  
Docking Studies ◽  
Antioxidant Potential ◽  
Cam Assay ◽  
In Silico Docking ◽  
Trigonella Foenum Graecum ◽  
Tnf Α ◽  
Anti Inflammatory

Introduction: Inflammation is a vital reaction of the natural immune system that protects against encroaching agents. However, uncontrolled inflammation can lead to complications. Trigonella foenum-graecum is traditionally used as an anti-inflammatory herb. Objectives: The current study was conducted to explore the antioxidant, anti-inflammatory, and antiangiogenic potentials of Trigonella foenum-graecum seeds oil. Methods: Oil was extracted from seeds of Trigonella foenum-graecum by cold press method and labelled as TgSO. Phytochemical (GCMS, Folin-Ciocalteu method) and metal analyses were conducted to evaluate the metalo-chemical profile of TgSO. In vitro antioxidant assays (2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid and ferric reducing antioxidant power) were performed to assess its antioxidant potential. In vitro antimicrobial property was evaluated using the agar disc diffusion method and the safety profile of TgSO was assessed following OECD 425 guidelines. In vivo anti-inflammatory activity of TgSO was assessed in carrageenan, serotonin, histamine, formalin, and cotton pellet-induced oedema models. Serum TNF-α, superoxide dismutase (SOD) and, catalases (CAT) levels were assessed by ELISA kit while the effects on angiogenesis were assessed by chick chorioallantoic membrane (CAM) assay. Histopathological studies using excised paws were conducted to observe the effect of TgSO treatment at the tissue level. In silico docking studies were conducted to screen binding potential of identified compounds towards TNF- α. Results: Extraction by cold press yielded 16% of TgSO. Phytochemical analysis of TgSO through GC-MS showed the presence of eugenol, dihydrocoumairn, and heptadecanoic acid, tri- and tetradecanoic acid and hexadecanoic acid respectively. Total phenolic contents of TgSO were found to be 37.1 ± 0.91 mg/g gallic acid equivalent in Folin-Ciocalteu method. Metal analysis indicated the presence of different metals in TgSO. Findings of antioxidant models showed moderate antioxidant potential of TgSO. Findings of antimicrobial assays showed that TgSO was active against S. aureus, S.epidermidis, C. albicans, and A. niger. In vivo toxicity study data showed that TgSO was safe up to the dose of 5000 mg/kg. Data of oedema models showed significant (p < 0.05) reduction in oedema development in TgSO treated animals in both acute and chronic models. Histopathological evaluations of paws showed minimal infiltration with inflammatory cells in TgSO-treated animals. Treatment also significantly (p < 0.05) down-regulated TNF-α in serum and while levels of SOD and CAT were upregulated. CAM assay findings revealed antiangiogenic activity of TgSO. Findings of in silico docking studies showed that identified phytoconstituents have potential to bind with culprit cytokine. Conclusion: Data of that current study conclude that TgSO has antioxidant, anti-inflammatory, and antiangiogenic effects that validate its traditional uses. Moreover, the synergistic actions of different phytoconstituents are proposed to be responsible for the observed effects.

scholarly journals Facile Synthesis, Characterization and in Silico Docking Studies of Novel Thiazolidine-2,4-Dione-Based Mannich Base Bearing Furan/Thiophene Moiety as Promising Anti-Inflammatory Agents

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jean Baptiste Nkurunziza ◽  
Pierre Dukuziyaturemye ◽  
Edith Musabwa ◽  
Balakrishna Kalluraya
Keyword(s):  
In Silico ◽  
Mannich Base ◽  
Inflammatory Diseases ◽  
Mannich Bases ◽  
Docking Studies ◽  
Secondary Amines ◽  
Standard Drug ◽  
In Silico Docking ◽  
Thiophene Moiety ◽  
Anti Inflammatory

Mannich bases are compounds bearing a β-amino carbonyl moiety. They are formed in the Mannich reaction that consists of an amino alkylation of an acidic proton placed next to a carbonyl functional group by formaldehyde and a primary or secondary amine. Mannich base products are known for their curative properties such as anti-inflammatory, antibacterial, anticancer, antifungal, anthelmintic, anticonvulsant, analgesic, anti-HIV, antipsychotic, antiviral, and antimalarial activities. Further, thiazolidinedione derivatives have shown to be efficacious in inflammatory diseases as wide-ranging as psoriasis, ulcerative colitis and non-alcoholic steatohepatitis. In light of the above observations, new series of thiazolidine-2,4-dione based Mannich base derivatives were synthesized via a simple and catalyst-free procedure involving the condensation of thiazolidine-2,4-dione, formaldehyde and secondary amines in DMF solvent. The structures of the newly synthesized compounds were confirmed by their IR, 1H-NMR, and Mass spectra. The synthesized compounds were tested for their in silico anti-inflammatory activity by Docking studies against COX-2 enzyme (PDB: 1CX2). Compounds 4a and 4b showed good in silico anti-inflammatory properties comparable to that of standard drug Diclofenac and may be considered as promising candidates for the development of new anti-inflammatory agents.

Advances in Anti-inflammatory Activity, Mechanism and Therapeutic Application of Ursolic Acid

2021 ◽  
Vol 21 ◽  
Author(s):  
Mingzhu Luan ◽  
Huiyun Wang ◽  
Jiazhen Wang ◽  
Xiaofan Zhang ◽  
Fenglan Zhao ◽  
...  
Keyword(s):  
Ursolic Acid ◽  
Inflammatory Diseases ◽  
Kidney Diseases ◽  
Inflammatory Activity ◽  
Inflammatory Factors ◽  
Inflammatory Stimuli ◽  
Bowel Diseases ◽  
Anti Inflammatory

: In vivo and in vitro studies reveal that ursolic acid (UA) is able to counteract endogenous and exogenous inflammatory stimuli, and has favorable anti-inflammatory effects. The anti-inflammatory mechanisms mainly include decreasing the release of histamine in mast cells, suppressing the activities of lipoxygenase, cyclooxygenase and phospholipase, and reducing the production of nitric oxide and reactive oxygen species, blocking the activation of signal pathway, down-regulating the expression of inflammatory factors, and inhibiting the activities of elastase and complement. These mechanisms can open up new avenues for the scientific community to develop or improve novel therapeutic approaches to tackle inflammatory diseases such as arthritis, atherosclerosis, neuroinflammation, liver diseases, kidney diseases, diabetes, dermatitis, bowel diseases, cancer. The anti-inflammatory activity, the anti-inflammatory mechanism of ursolic acid and its therapeutic applications are reviewed in this paper.

scholarly journals IN SILICO DESIGN AND MOLECULAR DOCKING STUDIES OF SOME 1, 2-BENZISOXAZOLE DERIVATIVES FOR THEIR ANALGESIC AND ANTI-INFLAMMATORY ACTIVITY

2017 ◽  
Vol 9 (3) ◽  
pp. 133
Author(s):  
Sarath Sasi Kumar ◽  
Anjali T
Keyword(s):  
Molecular Docking ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Analgesic Activity ◽  
In Silico ◽  
Docking Studies ◽  
Inflammatory Activity ◽  
Nicotinic Acetylcholine ◽  
Cox 2 ◽  
Anti Inflammatory

Objective: In silico design and molecular docking of 1,2-benzisoxazole derivatives for their analgesic and anti-inflammatory activity using computational methods.Methods: In silico molecular properties of 1,2-benzisoxazole derivatives were predicted using various software’s such as Chemsketch, Molinspiration, PASS and Schrodinger to select compounds having optimum drug-likeness, molecular descriptors resembling those of standard drugs and not violating the ‘Lipinski rule of 5’. Molecular docking was performed on active site of nicotinic acetylcholine receptor (PDB: 2KSR) for analgesic activity and COX-2 (PDB: 6COX) for anti-inflammatory activity using Schrodinger under maestro molecular modelling environment.Results: From the results of molecular docking studies of 1,2-benzisoxazole derivatives, all the compounds showed good binding interactions with Nicotinic acetylcholine receptor and COX-2. Compounds 4a and 4c showed highest binding scores (-7.46 and-7.21 respectively) with nicotinic acetylcholine receptor and exhibited maximum analgesic activity. Compound 4a showed highest binding score (-7.8) with COX-2 and exhibited maximum anti-inflammatory activity.Conclusion: All the derivatives of 1,2-benzisoxazole showed good analgesic and anti-inflammatory activity as predicted using molecular docking on respective receptors.

scholarly journals Development, Optimisation and Evaluation of Ketoprofen Lipospheres

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 1853-1863
Author(s):  
Shubhra Rai ◽  
Gopal Rai ◽  
Ashish Budhrani
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Research Work ◽  
Extended Period ◽  
Entrapment Efficiency ◽  
Inflammatory Activity ◽  
Scanning Calorimetry ◽  
Anti Inflammatory

Lipospheres represent a novel type of fat-based encapsulation system produced for the topical drug delivery of bioactive compounds. The goal of this research work was to develop lipospheres, including ketoprofen applied for topical skin drug delivery. Ketoprofen lipospheres were formulated by melt emulsification method using stearic acid and Phospholipon® 90G. The lipospheres were analysed in terms of particle size and morphology, entrapment efficiency, Differential scanning calorimetry, In-vitro drug release, In-vivo (Anti-inflammatory activity). Outcomes of research revealed that particle size was found to be 9.66 µm and entrapment efficiency 86.21 ± 5.79 %. In-vivo, the study of ketoprofen loaded lipospheres formulation shows a higher plain formulation concentration in plasma (5.61 mg/mL). For dermis, ketoprofen retention was 27.02 ± 5.4 mg/mL for the lipospheres formulation, in contrast to that of the plain formulation group (10.05 ± 2.8 mg/mL). The anti-inflammatory effect of liposphere drug delivery systems was assessed by the xylene induced ear oedema technique and compared with marketed products. Finally, it seems that the liposphere drug delivery system possesses superior anti-inflammatory activity as compared to the marketed product gel consistencies. Liposphere may be capable of entrapping the medicament at very high levels and controlling its release over an extended period. Liposphere furnishes a proper size for topical delivery as well as is based on non-irritating and non-toxic lipids; it’s a better option for application on damaged or inflamed skin.

scholarly journals Oleuropein modulates over-proliferation of keratinocytes in mice with imiquimodmediated psoriasis and inhibits differentiation of TH17 cells through the JAK3/STAT3 axis

2020 ◽  
Author(s):  
Quan Shi ◽  
Qi He ◽  
Weiming Chen ◽  
Jianwen Long ◽  
Bo Zhang
Keyword(s):  
T Cells ◽  
In Silico ◽  
Th17 Cells ◽  
Skin Lesions ◽  
Docking Studies ◽  
Inflammatory Disorder ◽  
T Helper 17 ◽  
In Silico Docking

IntroductionOleuropein (OLP) is polyphenol obtained from olive oil; it is proved in Chinese traditional medicine for its use in disorders including autoimmune and inflammatory disorders. Psoriasis (PSR) is an autoimmune and inflammatory disorder triggered by T-helper-17 (Th17) cells.Material and methodsWe developed an imiquimod (IMQ)-mediated PSR model in mice to study the anti-inflammatory role of OLP in psoriasis. The mice were given 50 mg/kg and 100 mg/kg dose of OLP. Histology was done to assess the inflammation of lesions. Western blot analysis was done for JAK3/STAT3 in isolated T cells, expression of RORgt was done by RT-PCR. The In silico molecular docking studies were done for interaction of OLP with target protein STAT3 and JAK3.ResultsTreatment of OLP attenuated proliferation in IMQ-mediated keratinocytes, improved infiltration of CD3+ cells in the skin lesions and in CD4+ and CD8+ T cells and also ameliorated the levels of cytokines. In in vitro studies in isolated T cells, OLP blocked the differentiation of Th17 cells and also the levels of IL-17 and the JAK3/STAT3 pathway. The in silico docking showed that OLP had potential binding affinity with JAK3 and STAT3 which was parallel to in vivo and in vitro findings.ConclusionsOLP ameliorates psoriasis skin lesions by blocking Th17-mediated inflammation. OLP may be an interesting molecule for treating autoimmunity in psoriasis.

scholarly journals Biological Evaluation and Docking Analysis of Daturaolone as Potential Cyclooxygenase Inhibitor

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Abdur Rauf ◽  
Francesco Maione ◽  
Ghias Uddin ◽  
Muslim Raza ◽  
Bina S. Siddiqui ◽  
...  
Keyword(s):  
In Silico ◽  
Biological Evaluation ◽  
Inflammatory Activity ◽  
Active Constituent ◽  
Ligand Complex ◽  
Reference Drug ◽  
Paw Oedema ◽  
Anti Inflammatory ◽  
Dose Dependent

This study deals with the isolation of the active constituent(s) from a methanolic extract ofPistacia integerrimaJ. L. Stewart barks and it was also oriented to evaluate thein vivoandin silicoanti-inflammatory activity. By NMR and crystallography techniques, we have isolated a triterpenoid identified as daturaolone (compound1). This compound showedin vivoa significant and dose dependent (1–30 mg/kg) anti-inflammatory activity on carrageenan-induced mouse paw oedema (ED50= 10.1 mg/kg) and on acetic acid-induced writhing responses in mice (ED50= 13.8 mg/kg). In thein vivoexperiments, the effect of tested compound was also evaluated in presence of the reference drug diclofenac (1–30 mg/kg). Moreover,in silicoanalysis of receptor ligand complex shows that compound1interacts with cyclooxygenases (COXs) binding sites displaying an interesting interaction with COX-1. These findings suggest that compound1isolated fromP.integerrimapossessesin vivoanti-inflammatory and antinociceptive potentials, which are supportedin silicoby an interaction with COXs receptors.

scholarly journals Stauntonia hexaphylla leaf extract (YRA-1909) suppresses inflammation by modulating Akt/NF-κB signaling in lipopolysaccharide-activated peritoneal macrophages and rodent models of inflammation

2021 ◽  
Author(s):  
Jaeyong Kim ◽  
Gyuok Lee ◽  
Huwon Kang ◽  
Ji-Seok Yoo ◽  
Yongnam Lee ◽  
...  
Keyword(s):  
Leaf Extract ◽  
Inflammatory Diseases ◽  
Vascular Diseases ◽  
Peritoneal Macrophages ◽  
Inflammatory Activity ◽  
Dependent Manner ◽  
Inflammatory Stimuli ◽  
Anti Inflammatory

Background: Inflammation is emerging as a key contributor to many vascular diseases and furthermore plays a major role in autoimmune diseases, arthritis, allergic reactions, and cancer. Lipopolysaccharide (LPS), which is a component constituting the outer membrane of Gram-negative bacteria, is commonly used for an inflammatory stimuli to mimic inflammatory diseases. Nuclear factor-kappa B (NF-κB) is a transcription factor and regulates gene expression particularly related to the inflammatory process. Stauntonia hexaphylla (Lardizabalaceae) is widely used as a traditional herbal medicine for rheumatism and osteoporosis and as an analgesic, sedative, and diuretic in Korea, Japan, and China. Objective: The purpose of this study was to investigate the anti-inflammatory activity of YRA-1909, the leaf aqueous extract of Stauntonia hexaphylla using LPS-activated rat peritoneal macrophages and rodent inflammation models. Results: YRA-1909 inhibited the LPS-induced nitric oxide (NO) and proinflammatory cytokine production in rat peritoneal macrophages without causing cytotoxicity and reduced inducible NO synthase and prostaglandin E2 levels without affecting the cyclooxygenase-2 expression. YRA-1909 also prevented the LPS-stimulated Akt and NF-κB phosphorylation and reduced the carrageenan-induced hind paw edema, xylene-induced ear edema, acetic acid-induced vascular permeation, and cotton pellet-induced granuloma formation in a dose-dependent manner in mice and rats. Conclusions: S. hexaphylla leaf extract YRA-1909 had anti-inflammatory activity in vitro and in vivo that involves modulation of Akt/NF-κB signaling. Thus, YRA-1909 is safe and effective for the treatment of inflammation.

scholarly journals Anti-Inflammatory and Analgesic Potential of Chromolaena odorata: A Review

2021 ◽  
Vol 6 (9) ◽  
pp. 8-16
Author(s):  
Ali Sandi Dwi Cahyo ◽  
Sri Oktavia ◽  
Ifora Ifora
Keyword(s):  
Analgesic Activity ◽  
Inflammatory Diseases ◽  
Inflammatory Activity ◽  
Bibliographic Databases ◽  
Sources Of Information ◽  
Chromolaena Odorata ◽  
Healing Agent ◽  
Anti Inflammatory

Inflammatory diseases have affected a large proportion of the population worldwide, and inflammation is a major risk factor for several dangerous disease pathologies. The increasing incidence and impact of inflammatory diseases have prompted research into pharmacological strategies to deal with them. Chromolaena odorata is traditionally used as an anti-inflammatory, antipyretic, antioxidant, analgesic, and as a wound-healing agent. Therefore, this review aimed to obtain a comprehensive review of the anti-inflammatory activity of Chromolaena odorata. This review provides evidence in the literature for the anti-inflammatory and analgesic activity of Chromolaena odorata, from 2010 to 2021. Three bibliographic databases were used as primary sources of information (PubMed, ScienceDirect, and Google Scholar). The keywords in this research were "Anti-inflammatory", "Analgesic" and "Chromolaena odorata". A total of 7 studies were included in this review according to the required criteria, 3 of which were in vitro studies and 4 in vivo studies.Pharmacological studies reported that Chromolaena odorata was proven to have anti-inflammatory activity by inhibiting NO, NF-κβ, p38 MAPK, IL-1β, TNF-α, suppressed leukocyte cell migration, reduced of edema and Chromolaena odorata also was shown analgesic activity through significantly reduced stomach writhing and reduction pain sensation in rats. This review explains the potential importance of Chromolaena odorata as a natural anti-inflammatory and analgesic.

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