Potent Anti-inflammatory Agent Research Articles

Lycopene as a Potential Anti-inflammatory Therapeutic Agent for Temporomandibular Joint Disorders: A Narrative Review

ABSTRACT Temporomandibular joint disorder is a common condition characterized by jaw joint and muscle pain and its treatment is often multifaceted. While conventional treatment modalities exist for the same, interest has grown in exploring alternative therapies such as antioxidants for their potential analgesic properties. The prospective therapeutic use of lycopene, a naturally occurring antioxidant present in tomatoes and other fruits, as an anti-inflammatory therapeutic modality in the management of temporomandibular joint problems is examined in this narrative review.

Exploring anti-inflammatory non-essential oil metabolites in Mentha canadensis: Insights into neutrophil extracellular trap inhibition for functional health promotion

Mentha canadensis, commonly known as Canadian mint, has been utilized in herbal medicine for its menthol content, addressing digestive and respiratory issues. It also serves as a popular culinary herb, adding a refreshing minty flavor to dishes and beverages. However, research on its non-essential oils and their anti-inflammatory potential is lacking. This study utilized multi-informative molecular networking to comprehensively profile the non-essential oils of M. canadensis. Cinnamic acid derivatives were identified as potent anti-inflammatory agents, with high activity ratings. By analyzing the Molecular Networking (MN) database, fourteen metabolites were identified. Compounds within the bioactive MN clusters demonstrate significant inhibition of reactive oxygen species generation, playing a crucial role in the management of oxidative stress. These compounds also effectively suppressed the formation of neutrophil extracellular traps. In conclusion, salvianolic acid B (IC50: 0.08 μM) was promoted as the chemical marker of M. canadensis for its potential anti-inflammatory effect. This study pioneers the identification of anti-inflammatory metabolites in M. canadensis' non-essential oils, offering insights into its therapeutic properties and potential for health-centric culinary applications.

Amino Acid Compositions and In vitro Anti-inflammatory Properties of Cookies Produced from Wheat and Soybean Composite Flour

Composite flours were formulated from wheat and soybean and mixed together to formulate four blends WSY 1 (100%), WSY 2 (80%-20%), WSY 3 (70%-30%), WSY 4 (60%-40%), respectively to bake cookies. The cookies were investigated for their amino acid profiles, in vitro anti-inflammatory properties and consumer acceptability of the cookies using standard methods. The amino acid profiles of the cookies were well established with high biological values (>70%) in terms of their essential, non-essential and hydrophobic amino acids while glutamic acid served as the most abundant amino acid (19.15 – 28.69%) present in each of the cookies. Moreso, the in-vitro anti-inflammatory properties of the cookies showed more potency with low IC50 (~20 \(\mu\)g/ml) than the standard sodium diclofenac, a well-known non-steroidal anti-inflammatory drug. Overall, the cookie sample from the 60% wheat and 40% soybean composite flour was acceptable to the consumers as shown by their ratings and perceptions, which could be highly found useful as potential bioactive antioxidant, anti-diabetic and anti-inflammatory agents in the management of chronic inflammations.

Development of novel nitric oxide production inhibitors based on the 7H-pyrrolo[2,3-d]pyrimidine scaffold.

Nitric oxide (NO), the smallest signaling molecule known, can be excessively produced by overexpressed inducible nitric oxide synthase (iNOS), and eventually leads to multiple inflammatory related diseases. Thus, reducing the overexpression of NO represents as very potential anti-inflammatory strategy. In current study, a series of compounds were designed and synthesized based on the hybridization of 7H-pyrrolo[2,3-d]pyrimidine and cinnamamide fragments in order to develop novel NO production inhibitors. Among them, compound S2h displayed a vigorous inhibitory activity on NO production with an IC50 value of 3.21 ± 0.67 µM, which was much lower than that of the positive control Nω-nitro-L-arginine (L-NNA, IC50 = 28.36 ± 3.13 µM). Due to its obeying Lipinski's and Veber's rules that guarantee compounds with good oral bioavailability, S2h effectively suppressed the paw swelling in carrageenan-induced mice. Additionally, compound S2h formed clear interactions with iNOS protein according to the docking analysis. Therefore, compounds S2h is a promising lead compound for further development of potent iNOS inhibitors or anti-inflammatory agents.

Activity of hydrogel-vitamin D3 /bacterioruberin nanoparticles on imiquimod-induced fibroblasts-keratinocytes spheroids

Topical administration of vitamin D3 (VD3) analogs and corticosteroids is the mainstay treatment for mild localized psoriasis. VD3 however is an unstable class II drug (insoluble and permeable), classically formulated as unattractive viscous and oil-based ointments or creams. In this work, nanostructured archaeolipid carriers (NAC) with a core loaded with VD3 and the C50 dipolar carotenoid from halophilic archaea bacterioruberin (BR): NAC-VD3, were formulated into a carbopol hydrogel: gNAC-VD3. After its rheological characterization, its anti-inflammatory and antioxidant activity was assessed on bi-cellular spheroids, consisting of a core of fibroblasts surrounded by a ring of keratinocytes activated with imiquimod (IMQ) as a psoriasis model. gNAC-VD3 (0.8 mg VD3/135 μg BR/gram gel) conserved the antioxidant activity, showed pseudoplastic non-Newtonian behaviour, stability over time, good occlusion capacity and spreadability, all suitable properties for topical application in patients with psoriasis. gNAC-VD3 did not decrease the viability of spheroids but significantly reduced the release of proinflammatory cytokines (IL-8, IL-6, TNF-α), oxidative stress (ROS), and matrix metalloproteinases from IMQ-induced spheroids to levels similar to the uninduced spheroids. Results suggest that gNAC-VD3 may constitute a potential anti-inflammatory agent for the topical treatment of mild psoriasis and deserves further in vivo exploration.

Design, synthesis and bioactivity evaluation of 4-hydroxycoumarin derivatives as potential anti-inflammatory agents against acute lung injury and colitis

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.

Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders.

Pregnane neuroactive steroids, notably allopregnanolone and pregnenolone, exhibit efficacy in mitigating inflammatory signals triggered by toll-like receptor (TLR) activation, thus attenuating the production of inflammatory factors. Clinical studies highlight their therapeutic potential, particularly in conditions like postpartum depression (PPD), where the FDA-approved compound brexanolone, an intravenous formulation of allopregnanolone, effectively suppresses TLR-mediated inflammatory pathways, predicting symptom improvement. Additionally, pregnane neurosteroids exhibit trophic and anti-inflammatory properties, stimulating the production of vital trophic proteins and anti-inflammatory factors. Androstane neuroactive steroids, including estrogens and androgens, along with dehydroepiandrosterone (DHEA), display diverse effects on TLR expression and activation. Notably, androstenediol (ADIOL), an androstane neurosteroid, emerges as a potent anti-inflammatory agent, promising for therapeutic interventions. The dysregulation of immune responses via TLR signaling alongside reduced levels of endogenous neurosteroids significantly contributes to symptom severity across various neuropsychiatric disorders. Neuroactive steroids, such as allopregnanolone, demonstrate efficacy in alleviating symptoms of various neuropsychiatric disorders and modulating neuroimmune responses, offering potential intervention avenues. This review emphasizes the significant therapeutic potential of neuroactive steroids in modulating TLR signaling pathways, particularly in addressing inflammatory processes associated with neuropsychiatric disorders. It advances our understanding of the complex interplay between neuroactive steroids and immune responses, paving the way for personalized treatment strategies tailored to individual needs and providing insights for future research aimed at unraveling the intricacies of neuropsychiatric disorders.

Design, synthesis and molecular modeling of novel D-ring substituted steroidal 4,5-dihydropyrazole thiazolinone derivatives as anti-inflammatory agents by inhibition of COX-2/iNOS production and down-regulation of NF-κB/MAPKs in LPS-induced RAW264.7 macrophage cells

It has been reported that 4,5-dihydropyrazole and thiazole derivatives have many biological functions, especially in the aspect of anti-inflammation. According to the strategy of pharmacophore combination, we introduced thiazolinone and dihydropyrazole moiety into steroid skeleton to design and synthesize a novel series of D-ring substituted steroidal 4,5-dihydropyrazole thiazolinone derivatives, and assessed their in vitro anti-inflammatory profiles against Lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophage cells. The anti-inflammatory activities assay demonstrated that compound 12e was considered as the most effective anti-inflammatory drug, which suppressed the expression of pro-inflammatory mediators including nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), it also dose-dependently inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-induced RAW 264.7 macrophage cells. Furthermore, the results of the Western blot analysis showed a correlation between the inhibition of the Nuclear factor-kappa B (NF-κB) and Mitogen-activated protein kinases (MAPKs) signaling pathways and the suppressive effects of compound 12e on pro-inflammatory cytokines. Molecular docking studies of compound 12e into the COX-2 protein receptor (PDB ID: 5IKQ) active site was performed to rationalize their COX-2 inhibitory potency. The results were found to be in line with the biological findings as they exerted more favorable interactions compared to that of dexamethasone (DXM), explaining their remarkable COX-2 inhibitory activity. The findings revealed that these candidates could be identified as potent anti-inflammatory agents, compound 12e could be a promising drug for the treatment of inflammatory diseases.

Synthesis, Molecular Docking Studies and Biological Evaluation of Thiazolyl Hydrazone Derivatives of Chromone-3-carbaldehyde as Potent Anti-Oxidant and Anti-Inflammatory Agents.

A series of 15 thiazolyl hydrazone derivatives of chromone-3- carbaldehyde have been designed and synthesized by the cyclization of thiosemicarbazone derivatives of chromone-3-carbaldehydes with 4'-substituted-2-bromo acetophenones. All these derivatives were evaluated for antioxidant activity by their direct scavenging activity objects to reactive oxygen species such as DPPH, and nitric oxide, as well as in vitro antiinflammatory activity by a protein denaturation method. Most of these synthesized compounds have shown significant antioxidant activity, among which the compounds 5b, 5c, 5e, 5g, and 5j showed very good antioxidant activities in comparison with the standard ascorbic acid. The in vitro anti-inflammatory activity revealed that the compounds 5b, 5g, and 5h possessed significant activity compared to standard diclofenac sodium. Additionally, molecular docking studies of these molecules using ovalbumin as the protein showed remarkable interactions with its active site residues, and the results indicated that the binding mode of these compounds closely resembled that of the reference compound, diclofenac sodium. Thus, these compounds represent an attractive template for the evaluation of new antiinflammatory and antioxidant agents and might be useful for exploring new therapeutic tools.

NMI-SO2Cl2-Mediated Amide Bond Formation: Facile Synthesis of Some Dihydrotriazolopyrimidine Amide Derivatives as Potential Anti-Inflammatory and Anti-Tubercular Agents.

Facile access to some novel biologically relevant dihydrotriazolopyrimidine carboxylic acid-derived amide analogues using NMI/SO2Cl2, and aromatic and aliphatic primary and secondary amines, is reported herein. The role of N-methylimidazole (NMI) as the base and sulfuryl chloride (SO2Cl2) as the coupling reagent has been effectively realized in accessing these molecules in good to excellent yields. The feasibility of the developed protocol has also been extended to the gram-scale synthesis of N-benzylbenzamide in a 75% yield from benzoic acid and benzyl amine. The newly synthesized compounds were tested via in vitro anti-inflammatory and anti-tubercular activity studies. The compounds 6aa and 6be were found to be the most active anti-inflammatory agents, whereas 6cb and 6ch were found to exhibit promising anti-tubercular potency when compared to other synthesized molecules. The structure-activity relationship (SAR) studies revealed the importance of the presence of electron-donating functionalities in enhancing the anti-inflammatory potential of the newly synthesized molecules. However, the presence of electron-withdrawing substituents was found to be significant for improving their anti-tubercular potency.

Optimization of Pressurized Liquid Extraction (PLE) Parameters for Extraction of Bioactive Compounds from Moringa oleifera Leaves and Bioactivity Assessment.

Moringa oleifera leaves are rich sources of bioactive compounds with potential health benefits, including antioxidants and anti-inflammatory agents. Pressurized liquid extraction (PLE) stands out as a promising technique for effectively extracting valuable compounds from natural sources. In this study, we aimed to optimize PLE parameters, such as temperature, extraction duration, and pressure, to maximize bioactive compound (polyphenols, flavonoids, and ascorbic acid) yield from M. oleifera leaves and evaluate their antioxidant and anti-inflammatory activities. According to the outcomes of this research, the maximum achieved total polyphenol content was 24.10 mg gallic acid equivalents (GAE)/g of dry weight (dw), and the total flavonoid content was increased up to 19.89 mg rutin equivalents (RtE)/g dw. Moreover, after HPLC-DAD analysis, neochlorogenic and chlorogenic acids, catechin and epicatechin, rutin, and narirutin were identified and quantified. As far as the optimum ascorbic acid content is concerned, it was found to be 4.77 mg/g dw. The antioxidant activity was evaluated by three different methods: ferric reducing antioxidant power (FRAP), the DPPH method, and the anti-hydrogen peroxide activity (AHPA) method, resulting in 124.29 μmol ascorbic acid equivalent (AAE)/g dw, 131.28 μmol AAE/g dw, and 229.38 μmol AAE/g dw values, respectively. Lastly, the albumin denaturation inhibition was found to be 37.54%. These findings underscore the potential of PLE as an efficient extraction method for preparing extracts from M. oleifera leaves with the maximum content of bioactive compounds.

Novel Piperazine Derivatives as Potent Antihistamine, Anti-Inflammatory, and Anticancer Agents, their Synthesis and Characterization.

In this study, a series of novel piperazine derivatives were synthesised with high-to-good yields, and their structural analogies were confirmed using FTIR, 1H-NMR, and LC-MS techniques. The synthesised compounds were evaluated for antioxidant and antimicrobial activities. Among the four synthesised piperazine derivatives, compound PD-2 exhibited relatively good antioxidant activity, with an IC50 value of 2.396 μg/mL, while the other three derivatives showed moderate to low antioxidant activity. Furthermore, compound PD-2 displayed antimicrobial activity against Pseudomonas aeruginosa, a gram-negative bacterium, and Candida albicans, a fungus. However, all four compounds showed strong resistance against grampositive bacteria, Staphylococcus aureus. Additionally, compound PD-1 exhibited significant antihistamine activity, eliciting an 18.22% reduction in histamine levels. Both PD-1 and PD-2 demonstrated noteworthy anti-inflammatory activity in a dosedependent manner (5-10μM), leading to the inhibition of nitrite production up to 39.42% and 33.7% at higher concentrations (10 μM) and inhibition of tumour necrosis factor-alpha (TNF-α) generation up to 56.97% and 44.73% at 10 μM, respectively. Additionally, both novel molecules PD-1 and PD-2 effectively restrained the growth of HepG2 cells in a manner that is dependent on the dosage up to 55.44% and 90.45% at the highest concentrations (100 μg/mL), respectively. These findings substantiate the rationale for further investigation into the novel series of persuasive piperazine analogues as potential agents with anti-inflammatory, antihistamine and anticancer properties.

Novel Schiff base derivatives containing 4,5-disubstituted thiazole as potential antibiofilm, anti-inflammatory and antioxidant agents: Green synthesis, molecular docking and ADME analysis

We report the microwave-assisted (MW) green synthesis of some novel 4,5 disubstituted thiazole-containing Schiff base derivatives (SBs) as antibiofilm, anti-inflammatory, and antioxidant agents. Spectroscopic techniques were used to confirm the formation of synthesized compounds. In-vitro antibiofilm and antifungal activity of synthesized molecules were evaluated against the Candida albicans strain (MTCC 227) by broth dilution method. Among the tested molecules, 3a showed excellent inhibition of both biofilm formation and planktonic growth at much lower MIC50 values (5.56 μg/mL and 1.20 μg/mL respectively) than other derivatives. Moreover, the spot assay of compound 3a showed fungicidal activity (100% cell death) for biofilm formation and planktonic growth at the lowest MFC values (10 μg/mL and 3.12 μg/mL respectively) compared to the standard drug fluconazole. In addition, the biofilm inhibition was further confirmed by morphological study through FESEM analysis. The anti-inflammatory study of SBs by protein denaturation method indicates that compound 3a (63.19%) was the most active anti-inflammatory agent at a lower concentration of 100 μg/mL in the series than the standard ibuprofen (42.36%). Whereas, the antioxidant study of SBs by the DPPH scavenging method shows compound 3j (IC50 = 436.10 μg/mL) was the more potent antioxidant agent as compared to other tested compounds and standard drug ascorbic acid (IC50 = 626.99 μg/mL). Furthermore, the molecular docking study of SBs with the active sites of sterol 14-α demethylase CYP51 enzyme of (PDB:5TZ1) C. albicans shows strong binding properties, supporting the experimental results of inhibition of biofilm formation. Additionally, the ADME characteristic of SBs demonstrates their potential for development as oral medication candidates.

Discovery of new 2-(3-(naphthalen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl)thiazole derivatives with potential analgesic and anti-inflammatory activities: In vitro, in vivo and in silico investigations

Joining the global demand for the discovery of potent NSAIDs with minimized ulcerogenic effect, new pyrazole clubbed thiazole derivatives 5a-o were designed and synthesized. The new derivatives were initially evaluated for their analgesic activity. Eight compounds 5a, 5c, 5d, 5e, 5f, 5h, 5m, and 5o showed higher activity than Indomethacin (potency = 105–130 % vs. 100 %). Subsequently, they were picked for further evaluation of their anti-inflammatory activity, ulcerogenic liability as well as toxicological studies. Derivatives 5h and 5m showed a potential % edema inhibition after 3 h (79.39 % and 72.12 %, respectively), with a promising safety profile and low ulcer indices (3.80 and 3.20, respectively). The two compounds 5h and 5m were subjected to in vitro COX-1 and COX-2 inhibition assay. The candidate 5h showed nearly equipotent COX-1 inhibition (IC50 = 38.76 nM) compared to the non-selective reference drug Indomethacin (IC50 = 35.72 nM). Compound 5m expressed significant inhibitory activities and a higher COX-2 selectivity index (IC50 = 87.74 nM, SI = 2.05) in comparison with Indomethacin (SI = 0.52), with less selectivity than Celecoxib (SI = 8.31). Simulation docking studies were carried out to gain insights into the binding interaction of compounds 5h and 5m in the vicinity of COX-1 and COX-2 enzymes that illustrated the importance of pyrazole clubbed thiazole core in hydrogen bonding interactions. The thiazole motif of compounds 5h and 5m exhibited a well orientation toward COX-1 Arg120 key residue by hydrogen bonding interactions. Compound 5h revealed an additional arene-cation interaction with Arg120 that could rationalize its superior COX-1 inhibitory activity. Compounds 5h and 5m overlaid the co-crystallized ligand Celecoxib I differently in the active site of COX-2. Compound 5m showed an enhanced accommodation with binding energy of − 6.13 vs. − 1.70 kcal/mol of compounds 5h. The naphthalene ring of compound 5m adopted the Celecoxib I benzene sulfonamide region that is stabilized by hydrogen-arene interactions with the hydrophobic sidechains of the key residues Ser339 and Phe504. Further, the core structure of compound 5m, pyrazole clubbed thiazole, revealed deeper hydrophobic interactions with Ala513, Leu517 and Val509 residues. Finally, a sensitive and accurate UPLC-MS/MS method was developed for the simultaneous estimation of some selected promising pyrazole derivatives in rat plasma. Accordingly, compounds 5h and 5m were suggested to be promising potent analgesic and anti-inflammatory agents with improved safety profiles and a novel COX isozyme modulation activity.

Structural characterization and anti-inflammatory activities of a purified polysaccharide from fruits remnants of Alpinia zerumbet (Pers.) Burtt. et Smith

We reported here an interesting source of Alpinia zerumbet Polysaccharides (named AZPs) from the residues after extracting essential oil by steam distillation from Alpinia zerumbet fructus. After a series of purifications, a homogeneous polysaccharide (AZP-2) of molecular weight 1.25 × 105 Da was obtained. Structure, anti-inflammatory activity, and anti-inflammatory mechanism were investigated. AZP-2 was mainly composed of galactose, arabinose, xylopyranose, glucose, and galacturonic acid. The main linkage structure of AZP-2 was determined after integrating the nuclear magnetic resonance (NMR) and methylation analysis, and the structure was comparatively complex. The results indicated that AZP-2 significantly decreased the production of NO and ROS in the inflammatory model established by lipopolysaccharide (LPS) stimulated RAW264.7, particularly at the concentration of 200 μg/mL. Furthermore, AZP-2 significantly modulated the secretion of both pro-inflammatory and anti-inflammatory cytokines. Notably, the mechanism of AZP-2 exhibiting inhibitory effects was related to regulating the NF-κB signaling pathway. Overall, AZP-2 could be used as a potential anti-inflammatory agent for further in-depth studies.

Protective Effect of Resveratrol Combined with Levodopa Against Oxidative Damage in Dopaminergic Neurons.

Levodopa (L-3,4-dihydroxyphenylalanine, L-Dopa) alleviates the symptoms of Parkinson's disease (PD), yet prolonged usage may give rise to severe adverse effects. Resveratrol (RSV) is a potent antioxidant, anticancer and anti-inflammatory agent. And a variety of polyphenol antioxidant compounds derived from RSV combined with levodopa have demonstrated neuroprotective activity against neuronal cell death. The purpose of this study was to examine the impact of this combination of RSV and L-Dopa on the survival rate, growth status, and reactive oxygen species (ROS) of MES23.5 dopamine (DA) neuron cells. In this study, we induced MPP+ in MES23.5 dopamine neuron cells and observed their survival rate, growth status, ROS content, as well as the effect of RSV combined with L-Dopa on cell survival. We also measured malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity levels as indicators of mitochondrial function, oxidative stress, and oxidative damage in the cells. Our results indicated that the MES23.5 dopamine neurons had decreased survival, poor growth status, and increased ROS content after MPP+ induction. Moreover, we found that MDA levels were elevated, and SOD activity levels were decreased, suggesting that the cells experienced abnormal mitochondrial function. However, when RSV was combined with L-Dopa, the cells showed a reduced level of MPP + -induced oxidative damage, with a more significant inhibitory effect observed in the RSV group at a concentration of 50 μmol/L. In conclusion, we found that the effects of co-administration of RSV with L-Dopa (100 μmol/L) was more effective than L-Dopa administered at the high dose. Thus, we found that RSV has the potential to reduce the dose of L-Dopa required to improve PD symptoms.

Design, synthesis, biological assessment and molecular modeling studies of novel imidazothiazole-thiazolidinone hybrids as potential anticancer and anti-inflammatory agents

A new series of imidazothiazole derivatives bearing thiazolidinone moiety (4a-g and 5a-d) were designed, synthesized and evaluated for potential epidermal growth factor receptor (EGFR) kinase inhibition, anticancer and anti-inflammatory activity, cardiomyopathy toxicity and hepatotoxicity. Compound 4c inhibited EGFR kinase at a concentration of 18.35 ± 1.25 µM, whereas standard drug erlotinib showed IC50 value of 06.12 ± 0.92 µM. The molecular docking, dynamics simulation and MM-GBSA binding energy calculations revealed strong interaction of compound 4c with binding site of EGFR. The synthesized compounds were evaluated for their anticancer activity by MTT assay against three human cancer cell lines A549 (Lung), MCF-7 (Breast), HCT116 (Colon), one normal human embryonic kidney cell line HEK293 and also for their EGFR kinase inhibitory activity. Few compounds of the series (4a, 4b, 4c) showed promising growth inhibition against all the tested cancer cell lines and against EGFR kinase. Among these, compound 4c was found to be most active and displayed IC50 value of 10.74 ± 0.40, 18.73 ± 0.88 against cancer cell lines A549 and MCF7 respectively whereas it showed an IC50 value of 96.38 ± 1.79 against HEK293 cell line indicating lesser cytotoxicity for healthy cell. Compounds 4a, 4b and 4c were also examined for their apoptosis inducing potential through AO/EB dual staining assay and it was observed that their antiproliferative activity against A549 cells is mediated via induction of apoptosis. Cardiomyopathy studies showed normal cardiomyocytes with no marked sign of pyknotic nucleus of compounds 4b and 4c. Hepatotoxicity studies of compounds 4b and 4c also showed normal architecture of hepatocytes. Compounds 4a-g and 5a-d were also evaluated for their in-vitro anti-inflammatory activity by protein albumin denaturation assay. Among the tested compounds 4a-d and 5a-b showed promising activity and were selected for in-vivo inflammatory activity against carrageenan rat paw edema test. Among these compounds, 4b was found to be most active in the series showing 84.94% inhibition, whereas the standard drug diclofenac sodium showed 84.57% inhibition. Compound 4b also showed low ulcerogenic potential and lipid peroxidation. Thus, compounds 4c and 4b could be a promising lead compounds for developing anticancer and anti-inflammatory agents with low toxicity and selectivity.

In-silico validation of cinnamaldehyde as potent anti-inflammatory agent coupled with potential in-vitro anti-cathepsin B and serum protein activities

<i>In-silico</i> validation of cinnamaldehyde as potent anti-inflammatory agent coupled with potential <i>in-vitro</i> anti-cathepsin B and serum protein activities

Green Synthesis of Mimosa pudica-Mediated Strontium Nanoparticles and its Anti-Inflammatory Activity

ABSTRACT Background: Considerable focus has been directed toward green synthesis as a dependable, sustainable, and environmentally friendly approach for synthesizing various nanomaterials. Mimosa pudica, a quickly grown pantropical weed, has been used widely for its anti-inflammatory and antimicrobial activity in traditional medicine. The development of strontium-based nanoparticles and nanoparticles linked with strontium has garnered attention in recent years due to their established utility in diverse domains such as effective drug distribution, bioimaging, cancer treatment, and advancements in bone engineering. Aims and Objectives: To examine the green synthesise of strontium nanoparticles using Mimosa pudica and its anti-inflammatory activity. Material and Methods: Mimosa pudica-mediated strontium nanoparticles’ anti-inflammatory activity was tested using bovine serum albumin denaturation assay, egg albumin denaturation assay, and membrane stabilization assay with diclofenac sodium as the standard. Result: In all three assays, increasing concentration of Mimosa pudica-mediated strontium nanoparticles exhibited an increasing anti-inflammatory effect, which was similar to the standard diclofenac sodium. Conclusion: Consequently, this holds promise as a new potential anti-inflammatory agent in forthcoming applications.

Review on Pyrazole Hybrids as Anti-microbial Agents

Abstract: A five-membered heteroaromatic ring with two nitrogen atoms, pyrazole, is of immense significance. Pyrazole and its derivatives are well-known nitrogen-containing heterocyclic compounds that are significant in medicinal chemistry and have a variety of biological properties, according to a thorough analysis of this class of heterocyclic lead. This article summarises some biologically active, potent pyrazole hybrids and their structure-activity relationship for antimicrobial activity published by various researchers across the world. It is divided into two sections. The first part summarizes recent developments in pyrazole derivatives for various biological activities, such as anti-Alzheimer’s, antioxidant, anticancer, anti-inflammatory, and antiviral, while the second section focuses on a detailed substitution analysis of pyrazole with its hybrid, which is the structure-activity relationship needed for antimicrobial activity. The presence of pharmacological potential of pyrazole moiety has been demonstrated by the role of a nucleus in pharmacological agents from different therapeutic groups, such as the potent anti-inflammatory agent celecoxib, anti-obesity drug rimonabant, analgesic diphenamizole, H2-receptor agonist betazole, and antidepressant agent fezolamide. The design of new pyrazole derivatives has become an interesting research area due to their versatile nature and biological significance. Moreover, it has been observed that pyrazole in combination with another moiety has a strong potent antimicrobial effect.