Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry - Online First
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The Structural Analogy of MASP-2 with Thrombin and MASP-1 Reveals Strong Binding with PAR4
Authors: Uzma Saqib, Mridul Madhuri, Sumati Hajela, Sadhana Sharma and Krishnan HajelaAvailable online: 20 January 2026More LessIntroductionThe historical discovery that thrombin activates Protease-Activated Receptor 4 (PAR4) has paved the way for several novel findings. Besides thrombin, the complement lectin pathway protease Mannose-Binding Lectin-Associated Serine Protease-1 (MASP-1) also binds to PAR4, albeit with lower affinity. Similar to thrombin, MASP-1 activates Ca2+ signaling pathways in endothelial cells. MASP-2, a homolog of MASP-1, plays an important role in complement activation; however, its direct interaction with PAR4 has not yet been elucidated. In this study, we performed structural investigations of thrombin, MASP-1, and MASP-2 to evaluate their binding affinities toward the PAR4 peptide.
MethodsWe employed in silico docking, binding affinity calculations, molecular dynamics simulations, and mutagenesis studies to test our hypothesis.
ResultsFor the first time, we demonstrate that, like thrombin and MASP-1, MASP-2 binds to PAR4 with appreciable affinity and could serve as a potential agonist of the PAR4 receptor and its associated inflammatory signaling pathways.
DiscussionThe high sequence similarity of MASP-2 with MASP-1 and thrombin is an important factor in attaining comparable binding with the PAR4 peptide.
ConclusionOur findings may pave the way for future investigations into the signaling mechanisms and therapeutic potential of PAR4-mediated inflammatory diseases.
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Design, Spectral Insights, and Enhanced Antioxidant Potential of Novel Phenothiazine Derivatives-1
Authors: Shamsher Singh, Himanchal Sharma, Smiriti Gohri and Dhananjay TaumerAvailable online: 02 January 2026More LessIntroductionPhenothiazine derivatives represent an important class of heterocyclic compounds known for a wide range of pharmacological activities. Their antioxidant potential has drawn considerable interest for therapeutic applications against oxidative stress-related disorders. This study focused on synthesizing a new series of phenothiazine derivatives and evaluating their antioxidant activity.
MethodsA series of phenothiazine derivatives [5a–5h] was synthesized by conjugating phenothiazine with various aryl amines via an acetyl linker using standard organic synthesis techniques. The structures of the synthesized compounds were confirmed using spectroscopic techniques, including FT-IR, ^1H NMR, ^13C NMR, and mass spectrometry (MS). Antioxidant activity was assessed using two in vitro assays: the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method and the low-density lipoprotein (LDL) oxidation inhibition assay.
ResultsAll synthesized compounds were successfully characterized by the aforementioned spectroscopic techniques. The antioxidant assays revealed that most of the derivatives exhibited notable antioxidant activity. Among them, Compound 5e, bearing a 4-amino-2-methoxyphenol moiety, demonstrated the highest activity, surpassing the standard antioxidants Vitamin C and butylated hydroxyanisole (BHA). Conversely, compound 5h showed comparatively lower activity.
DiscussionThe findings indicate that structural variations, particularly the presence of electron-donating groups on the phenothiazine ring, significantly influence antioxidant potential. The superior performance of Compound 5e highlights the importance of specific substituent patterns in enhancing biological activity. However, further investigation into pharmacokinetics and in vivo efficacy is necessary to support potential therapeutic use.
ConclusionThe study successfully synthesized and characterized a novel series of phenothiazine derivatives, several of which exhibited potent antioxidant properties. Structure–activity relationship (SAR) analysis suggested that electron-donating substituents enhance activity, pointing to promising future applications in treating oxidative stress-related conditions.
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Clinical Applications of Ligand Traps Targeting Activin Type II Receptors
Available online: 02 January 2026More LessThis review summarizes recent advances in ligand trap therapies targeting activin type II receptors [ActRIIA/ACVR2A and ActRIIB/ACVR2B], which serve as shared receptors for members of the TGF-β family, including activins, GDF11, and myostatin [MSTN]. These receptors mediate Smad2/3 signaling and play critical roles in hematopoiesis, vascular homeostasis, and muscle regulation. Two peptide-based ligand traps have recently received clinical approval: luspatercept [ActRIIB-Fc], an erythroid maturation agent, and sotatercept [ActRIIA-Fc], a novel therapeutic agent for pulmonary arterial hypertension [PAH]. Luspatercept primarily inhibits activin B and GDF11, thereby promoting late-stage erythropoiesis and demonstrating efficacy in anemia associated with conditions such as myelodysplastic syndromes [MDS] and β-thalassemia. Sotatercept binds activins and GDFs to rebalance Smad2/3 and Smad1/5/8 signaling, thereby improving vascular remodeling in PAH. Although both agents have failed to increase skeletal muscle mass in clinical trials consistently, they represent significant advances in the treatment of hematopoietic and vascular disorders. Future studies should focus on optimal dosing strategies, long-term safety, and potential synergistic effects when combined with other therapeutic modalities.
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Next-Generation Probiotics in Allergy Therapy: Scientific Evidence and Clinical Applications
Authors: Vatan Chaudhary, Atul Pratap Singh, Himanchal Sharma and Dhananjay TaumarAvailable online: 04 December 2025More LessThe global increase in allergic diseases, such as atopic dermatitis, allergic rhinitis, asthma, and food allergies, has become a major public health issue. These diseases typically involve immune dysregulation, including a Th1/Th2 imbalance, increased IgE levels, regulatory T cell (Treg) dysfunction, and epithelial barrier dysfunction. New research has recognised an important role for the gut and mucosal microbiome in regulating immune responses and has prompted interest in the therapeutic utility of probiotics. Probiotics are live microbes that, when given in adequate amounts, confer health benefits, generally such as immunomodulation or restoration of gut barrier function. Traditional probiotics (i.e., Lactobacillus and Bifidobacterium species) reduce allergic inflammation through promotion of Treg differentiation, increases in anti-inflammatory cytokines (e.g., IL-10), suppression of Th2 cytokines (e.g., IL-4), and modification of IFNγ. Traditional probiotics also support mucosal barrier function and restore microbial composition by producing short-chain fatty acids (SCFAs), like butyrate, which act directly on G-protein-coupled receptors and histone deacetylases to suppress inflammation. Next-generation probiotics (NGPs), such as Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides fragilis, and some clusters of Clostridia, can provide more targeted effects. These NGPs can secrete anti-inflammatory metabolite compounds, such as polysaccharide A (PSA), which modulate dendritic cells and increase Treg activity, and can promote mucin production to improve gut barrier function. Overall, there are key issues with strain specificity, dose, safety in immunocompromised individuals, and possible regulatory classification issues. Future opportunities may include precision microbiome profiling, synthetic biology, and artificial intelligence-driven strain discovery to develop personalised approaches to allergy immunotherapy.
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Isolation, Characterization, Molecular Docking, and Antioxidant Evaluation of Esculetin Derived from Cichorium intybus Seeds
Authors: Naina and Phool ChandraAvailable online: 03 October 2025More LessIntroductionCichorium intybus, a biennial plant belonging to the Asteraceae family, has been widely utilized in traditional Indian medicine for its tonic, anti-acne, anti-inflammatory, antioxidant, and hepatoprotective properties. Despite its known medicinal benefits, the bioactive compounds responsible for these activities require further exploration to validate their therapeutic potential. Our aim is to investigate the molecular docking interactions and antioxidant potential of an isolated bioactive compound from Cichorium intybus seeds, with a focus on its role in mitigating oxidative stress and inflammation in the liver.
MethodsThe compound was isolated using ethanol extraction, followed by phytochemical screening, TLC, column chromatography, and identification through FTIR, NMR, and mass spectroscopy. Molecular docking studies were conducted using Schrödinger Suite to analyze interactions with PPARα. Antioxidant activity was evaluated using DPPH and ABTS radical scavenging assays, with results compared through Trolox Equivalent Antioxidant Capacity (TEAC) values.
ResultsEsculetin, the isolated compound, exhibited strong binding affinity with PPARα (XP GScore: -7.0 kcal/mol). Antioxidant assays showed moderate activity, with DPPH radical scavenging activity (RSA) of 10.37% and ABTS RSA of 7.445%. The TEAC values were 13.23 μmol/mg and 21.930 μmol/mg, respectively, indicating its potential antioxidant efficacy.
DiscussionEsculetin from Cichorium intybus showed moderate antioxidant activity and strong PPARα binding, indicating its potential as a therapeutic agent. These findings align with existing research but require validation through in vivo studies to confirm efficacy and elucidate biological mechanisms.
ConclusionEsculetin demonstrates significant potential as a bioactive antioxidant and anti-inflammatory agent, supporting its relevance for further pharmacological and therapeutic investigations.
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Developments in the Management Strategies for Allergy: Advances in Artificial Intelligence and Future Perspectives
Authors: Suraj Kumar, Rishabha Malviya, Sathvik Belagodu Sridhar, Javedh Shareef and Tarun WadhwaAvailable online: 16 September 2025More LessIntroductionArtificial intelligence (AI) is rapidly transforming biomedical research by offering advanced tools to analyse complex datasets. In the field of allergy studies, however, the translation of AI-generated insights into clinical practice remains limited and underutilised.
MethodThis review critically discussed the current applications of AI in allergy studies. It focuses on the methodological foundations of AI, including machine learning and clustering algorithms, and assesses their practical benefits and limitations. Representative case studies are explored to demonstrate real-world applications, and challenges in data quality, integration, and algorithmic fairness are examined.
ResultsAI techniques have shown promise in tasks such as disease phenotyping and patient stratification within allergy research. Case studies reveal that AI can uncover immunological insights and support precision medicine approaches. However, the field faces challenges, including fragmented data sources, algorithmic bias, and the limited presence of therapeutic AI tools in clinical practice.
DiscussionDespite the demonstrated potential, several barriers hinder the broader adoption of AI in allergy care. These include the need for high-quality, standardised datasets, ethical oversight, and transparent methodologies. The review highlights the importance of these factors in ensuring the reliability, reproducibility, and equity of AI-driven interventions in allergy research.
ConclusionAI holds significant promise for improving diagnostic accuracy and enabling personalised treatment strategies in allergy care. Realising its full potential will require robust frameworks, ethical governance, and interdisciplinary collaboration to overcome current limitations and drive clinical translation.
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