Anti-inflammatory & anti-allergy agents in medicinal chemistry最新文献

{"title":"Isolation, Characterization, Molecular Docking, and Antioxidant Evaluation of Esculetin Derived from Cichorium intybus Seeds.","authors":"Naina, Phool Chandra","doi":"10.2174/0118715230393322250911114129","DOIUrl":"https://doi.org/10.2174/0118715230393322250911114129","url":null,"abstract":"<p><strong>Introduction: </strong>Cichorium 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.</p><p><strong>Methods: </strong>The 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.</p><p><strong>Results: </strong>Esculetin, 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.</p><p><strong>Discussion: </strong>Esculetin 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.</p><p><strong>Conclusion: </strong>Esculetin demonstrates significant potential as a bioactive antioxidant and antiinflammatory agent, supporting its relevance for further pharmacological and therapeutic investigations.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analytical Techniques for the Quantification and Validation of Resveratrol: A Review.","authors":"Harsh Goel, Kandasamy Nagarajan, Lalit Mohan Nainwal, Snigdha Bhardwaj","doi":"10.2174/0118715230403013250901204059","DOIUrl":"https://doi.org/10.2174/0118715230403013250901204059","url":null,"abstract":"<p><strong>Introduction: </strong>Trans-resveratrol is a bioactive polyphenol that has been widely studied for its antioxidant, anti-inflammatory, and chemoprotective properties. It holds promise in pharmaceutical and nutraceutical formulations but is limited by poor bioavailability and stability.</p><p><strong>Methods: </strong>This review synthesizes validated analytical methods for quantifying trans-resveratrol across various matrices. A comprehensive literature search (2000-2024) was conducted using PubMed, Scopus, and Google Scholar, focusing on RP-HPLC, HPTLC, GC, and UV spectroscopy. Method validation follows ICH guidelines.</p><p><strong>Results: </strong>Thirty-seven validated analytical methods were reviewed. RP-HPLC using C18 columns with acetonitrile-water mobile phases dominated the literature. The most sensitive technique identified was LC-MS/MS (LOD = 0.001 μg/mL), particularly effective in biological samples. Matrix types included wine, serum, and nanoparticle formulations.</p><p><strong>Discussion: </strong>RP-HPLC and LC-MS/MS have emerged as robust techniques for resveratrol quantification due to their sensitivity and specificity. Emerging tools like biosensors and UPLC offer rapid analysis with lower solvent consumption. Challenges such as isomerization, photodegradation, and matrix interferences necessitate stringent sample-handling protocols.</p><p><strong>Conclusion: </strong>Advanced chromatographic methods, especially RP-HPLC and LC-MS/MS, are essential for the reliable quantification of trans-resveratrol. Future research should focus on analytical standardization and the development of novel delivery systems to enhance resveratrol's pharmacokinetic profile.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developments in the Management Strategies for Allergy: Advances in Artificial Intelligence and Future Perspectives.","authors":"Suraj Kumar, Rishabha Malviya, Sathvik Belagodu Sridhar, Javedh Shareef, Tarun Wadhwa","doi":"10.2174/0118715230389406250906142050","DOIUrl":"https://doi.org/10.2174/0118715230389406250906142050","url":null,"abstract":"<p><strong>Introduction: </strong>Artificial 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.</p><p><strong>Method: </strong>This 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.</p><p><strong>Results: </strong>AI 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.</p><p><strong>Discussion: </strong>Despite 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.</p><p><strong>Conclusion: </strong>AI 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.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation and Evaluation of Amorphous Solid Dispersion of Etoricoxib, Employing A Fast Approach for Polymer Selection.","authors":"Bandenawaz M Shaikh, Jitendra W Gajbe, Ashwini R Madgulkar, Mangesh R Bhalekar, Minakshi B Shinde","doi":"10.2174/0118715230357451250812171047","DOIUrl":"https://doi.org/10.2174/0118715230357451250812171047","url":null,"abstract":"<p><strong>Background: </strong>Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage pain and inflammation but are associated with gastrointestinal and cardiovascular risks, especially with COX-2 inhibitors. Topical delivery systems offer a safer alternative by minimizing systemic exposure; however, poor solubility and limited skin penetration remain challenges. Enhancing solubility through solid dispersion and incorporating it into a gel formulation may improve permeability and therapeutic effectiveness, addressing the need for safer and more efficient topical NSAID delivery.</p><p><strong>Introduction: </strong>This investigation aimed to enhance the solubility and dissolution rate of poorly water-soluble etoricoxib through the development of solid dispersions using the kneading method.</p><p><strong>Method: </strong>A suitable carrier was selected from a pool of candidates based on polarised microscopy analysis. The influence of a solubilizer on amorphization was evaluated. Solid dispersions of Etoricoxib and its corresponding physical mixtures, incorporating or excluding the solubilizer, were prepared at varying drug-to-carrier ratios. Yield, drug content, saturation solubility, and in vitro dissolution profiles of these formulations were determined. Solid-state characterization using Fourier Transform-Infrared (FTIR), X-ray diffraction (XRD), Scanning electron microscopy (SEM), and differential scanning calorimetry (DSC) techniques was conducted.</p><p><strong>Result: </strong>FTIR spectra indicated the formation of intermolecular hydrogen bonds within the dispersions. XRD, SEM, and DSC analysis confirmed the amorphous transition of crystalline etoricoxib in all the prepared solid dispersions. In comparison to pure etoricoxib and its physical mixes, the produced solid dispersions showed significantly improved dissolution and solubility, Discussion: Solid dispersion technology effectively enhanced the solubility and dissolution of poorly water-soluble etoricoxib. Polarised microscopy also proved valuable for rapid excipient screening. However, the study was limited by the narrow range of solubilizers tested. While Poloxamer 407 was selected for its availability and untapped potential, broader screening of advanced solubilizers could offer improved outcomes.</p><p><strong>Conclusion: </strong>The solubility increased from 99.08 to 296.8 μg/ml and the dissolution rose from 69.32% to 98.07%. These findings suggest that the kneading method and Poloxamer successfully produced amorphous solid dispersions of etoricoxib with significantly enhanced solubility and dissolution properties, potentially improving its bioavailability.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization and In-Vitro Characterization of Tetrahydrocurcumin Loaded Niosome for Psoriasis Management.","authors":"Akash Garg, Chetan Singh Chauhan, Rohitas Deshmukh, Rutvi Agrawal","doi":"10.2174/0118715230385381250807024537","DOIUrl":"https://doi.org/10.2174/0118715230385381250807024537","url":null,"abstract":"<p><strong>Introduction: </strong>The low solubility and permeability of tetrahydrocurcumin act as a barrier in its therapeutic effectiveness, particularly in the topical treatment of skin diseases like psoriasis.</p><p><strong>Method: </strong>Niosomes were prepared using thin-film hydration method using span 60, cholesterol as independent variables in Box Behnken design. Particle size, entrapment efficiency and drug loading were taken as dependent variables. In Box Behnken design the levels are -1, 0, and +1. The values for span 60 are 50, 75, and 100mg and for cholesterol 10, 20, and 30mg.</p><p><strong>Results: </strong>The optimized formulation has a particle size of 116.9 nm, entrapment efficiency of 94.7% and, drug loading of 85.23%. The niosomes showed first-order release kinetics property and maintained stability at 4℃ and 25℃ for three months. The desirability score obtained was 0.896.</p><p><strong>Discussion: </strong>The optimized niosomal formulation enhanced THC's solubility, permeability, and stability, supporting its potential for effective topical psoriasis treatment. Future studies will focus on in situ gel incorporation and in vivo validation.</p><p><strong>Conclusion: </strong>The developed formulation significantly improves the solubility and permeability of tetrahydrocurcumin which leads to improved therapeutic effectiveness in the formulation for the treatment of psoriasis. Further studies will incorporate these niosomes in in situ gels for the application.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144985091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translational Horizons in Computer-Aided Drug Discovery: Bridging <i>In Silico</i> Insights with One Health Challenges.","authors":"Manos C Vlasiou","doi":"10.2174/0118715230424575250729093150","DOIUrl":"https://doi.org/10.2174/0118715230424575250729093150","url":null,"abstract":"","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Anti-Inflammatory Compounds from Kappaphycus Alvarezii in High Cholesterol-Induced Zebrafish Larvae: Revealing Cardiovascular Potential.","authors":"Rabika Ramalingam, Kaliyamurthi Venkatachalam, Ambika Binesh","doi":"10.2174/0118715230342356250611114954","DOIUrl":"https://doi.org/10.2174/0118715230342356250611114954","url":null,"abstract":"<p><strong>Introduction: </strong>The study investigated the anti-inflammatory properties of Kappaphycus alvarezii by employing zebrafish larvae as a model system.</p><p><strong>Materials and methods: </strong>The seaweed extract was subjected to phytochemical screening, uncovering the presence of alkaloids, terpenoids, proteins, and cardiac glycosides. UV-visible, FTIR, and GC-MS were employed to identify the presence of bioactive compounds. The western blotting method was used to confirm the target proteins.</p><p><strong>Results: </strong>Analysis through GC-MS revealed the presence of specific organic bioactive compounds, including 4-chlorobuten-3-yne, Methane-D, trichloro, and 1-propanol, 2-(1-methylethoxy), each with distinct retention times. In the group induced with a high-cholesterol diet (HCD), the activities of antioxidant enzymes (SOD, CAT, GPx, and GST) were elevated, and K. alvarezii treatment successfully reversed this effect. Additionally, the HCD group exhibited upregulation in the protein expression of MMP-9, MMP-13, MPO, IL-6, TNFα, and NFκB due to inflammation, whereas K. alvarezii therapy reversed the inflammatory process in the treated group. These findings indicate the potential of K. alvarezii to counteract inflammatory responses induced by a high-cholesterol diet through modulation of antioxidant enzyme activities and downregulation of pro-inflammatory markers.</p><p><strong>Conclusion: </strong>Kappaphycus alvarezii shows promise for developing natural sources for antiradicals, food supplements, nutraceuticals, and various functional foods with therapeutic applications.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Treatment with Angiotensin-(1-7) Improves Metabolism by Modulating Adipose Tissue and Oxidative Stress in Mice.","authors":"Alanna Fernandes Paraíso, Jaciara Neves Sousa, João Marcus Oliveira Andrade, Eloá Mangabeira Santos, Débora de Farias Lelis, Charles Santos Da Costa, Jones Bernardes Graceli, Bruna Kaicy Barbosa, Lucyana Conceição Farias, Alfredo Mauricio Batista de Paula, André Luiz Sena Guimarães, Daniele Teixeira Alves, Maik Gollasch, Robson Augusto Souza Santos, Sérgio Henrique Sousa Santos","doi":"10.2174/0118715230367867250613134043","DOIUrl":"https://doi.org/10.2174/0118715230367867250613134043","url":null,"abstract":"<p><strong>Background: </strong>Angiotensin-(1-7) is a crucial endocrine modulatory peptide that can enhance conditions like diabetes, obesity, and other features of metabolic syndrome. However, there is a lack of data on its long-term effects.</p><p><strong>Aim: </strong>This study aimed to assess the impact of chronic oral administration of Angiotensin- (1-7) on adipose tissue modulation and metabolic processes in mice.</p><p><strong>Methods: </strong>The Angiotensin-(1-7) peptide oral formulation was encapsulated within the hydroxypropyl-β-cyclodextrin oligosaccharide (HPβCD) matrix. Male Swiss mice were divided into 4 groups: standard diet (ST)+HPßCD; ST+Ang-(1-7); high-fat diet HFD+HPßCD, and HFD+Ang-(1-7). The treatment lasted for 12 months, during which body weight, food intake, glycemic and lipid profiles, visceral adiposity, oxidative stress indicators, histological parameters, quantitative real-time PCR assessments, and comprehensive in silico bioinformatics analyses were conducted.</p><p><strong>Results: </strong>Prolonged treatment with Ang-(1-7) led to improvements in glucose levels, visceral body adiposity, decreased cholesterol and triglyceride levels, and reduced oxidative stress. Bioinformatics analysis revealed that AKT1, an insulin signaling effector (INS), and key inflammatory markers like IL-6 and VEGF may be potential molecular mediators of Angiotensin-(1-7) effects. Non-obese animals treated with Angiotensin-(1-7) showed increased expression levels of AKT1, supporting the findings from the bioinformatics analysis.</p><p><strong>Conclusion: </strong>This study demonstrates that chronic oral use of Ang-(1-7) enhances adipose and metabolic parameters, suggesting its potential as a long-term therapeutic agent for regulating metabolic disorders.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Mouth Rinse Displaying Analgesic and Anti-inflammatory Properties: An in vitro Study.","authors":"Saravanan Sampoornam Pape Reddy, Delfin Lovelina Francis, Soumi Mondal, Manish Rathi, Neelima Katti, Sukhbir Singh Chopra","doi":"10.2174/0118715230384352250526103643","DOIUrl":"https://doi.org/10.2174/0118715230384352250526103643","url":null,"abstract":"<p><strong>Introduction: </strong>Periodontitis is a chronic inflammatory disease requiring effective anti-inflammatory treatments. Nano-silver and essential oils have shown potential due to their antimicrobial and anti-inflammatory properties. Combining these agents offers a promising therapeutic approach. This study investigated the cy-totoxic and anti-inflammatory properties of a novel essential oil compound contain-ing nanosilver using HaCaT and THP-1 human leukemia monocytic cell lines.</p><p><strong>Materials and methods: </strong>Neutral red uptake (NRU) assay was used to assess cyto-toxicity and ELISA to evaluate the inflammatory cytokines. The test compound was compared to 0.12% chlorhexidine gluconate (CHX). Cytotoxicity was determined in HaCaT and THP-1 cell lines using NRU assay. TNF-α expression was measured us-ing ELISA, and COX-2 inhibition assay was performed.</p><p><strong>Results: </strong>Cytotoxicity of the test compound was nearly absent. TNF-α levels de-creased in positive control (2.81pg/ml) and test samples (1.30 pg/ml) compared to control (22.04pg/ml). COX-2 inhibition assay revealed test compound (0-20%) and positive control (0-100%), with 25 μM celecoxib as a standard. IC50 for HaCaT cells was 0.6334% (positive control) and 0.6051% (test group). IC50 using THP-1 cells was not converged for the test and 424.6% for positive control. IC-50 for COX-2 inhibition was 1.469% in the test and 8.801% in the positive control.</p><p><strong>Discussion: </strong>This study showed the possibility of novel essential oils and nano-sil-ver-containing compounds as a medication material in preventing gingivitis. The cy-totoxicity was negligible, while the level of TNF- α was much decreased, and COX-2 activity assays indicated its efficiency in anti-inflammatory properties. The results encourage the therapeutic potential of the compound for periodontitis, and further studies are required to demonstrate therapeutic efficiency and safety.</p><p><strong>Conclusion: </strong>Results demonstrate the inhibitory effect of the test compound on COX-2 activity. The potential of a novel test compound containing essential oils and nano-silver as a promising anti-inflammatory agent warrants further investigation for its therapeutic applications in periodontitis.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inclusive Drug Designing of Novel Indole Derivatives using Rationale, Pharmacophore Mapping and Molecular Docking.","authors":"Anuradha Mehra, Amit Mittal, Rahul Sharma, Rekha Sangwan, Aryan Mehra","doi":"10.2174/0118715230352441250309014403","DOIUrl":"https://doi.org/10.2174/0118715230352441250309014403","url":null,"abstract":"<p><p>Introductions/Background: The presence of insufficient insulin signaling in type 2 diabetes arises due to either insulin resistance or impaired insulin secretion, ultimately lead-ing to elevated blood glucose levels, a condition known as hyperglycemia. Diabetes poses a pervasive worldwide challenge, with its prevalence steadily surging in both developed and developing nations. A promising avenue for improving the management of diabetes type 2 involves the exploration of glucokinase activators as an innovative therapeutic target. Nota-bly, a recent breakthrough in this area has been the market approval granted by the Japanese FDA for the use of the innovative GKA, Dorzagliatin, in the treatment of diabetes type 2.</p><p><strong>Objective: </strong>To augment the management of diabetes type 2 and mitigate the undesirable side effects linked to prolonged use of conventional medications, this research endeavor sought to create innovative glucokinase activators.</p><p><strong>Methods: </strong>The ZINC database yielded a collection of 56 compounds, each showcasing a 40% structural similarity to 1-(phenylsulfonyl)-1H-indole-2-carboxylic acid. These compounds, all featuring the distinctive indole core, were meticulously selected for further investigation. Structural illustrations were crafted using ChemBioDraw Ultra, and 1.5.6 AutoDock Vina was for molecular docking. The Swiss ADME algorithm facilitated online log P predictions, while the software PKCSM was utilized to forecast the toxicity profiles of the leading com-pounds. DFT analysis was done to ensure the stability of compounds by using Gaussian 16 quantum chemistry software and Mulliken charge distributions used to optimize molecular geometries.</p><p><strong>Results: </strong>Among all the compounds, RS33 and RS37 exhibited the highest affinities for GK receptors, with the docking scores of -8.93 and -8.44 kcal/mol, respectively. These com-pounds follow Lipinski's Rule, indicating promising absorption and excretion profiles through the gastrointestinal tract. Compared to standard drugs Dorzagliatin (GKA) and MRK (co-crystallized ligand), both RS33 and RS37 demonstrate no AMES toxicity, skin sensitiza-tion, and hepatotoxicity. RS43 is the most stable compound as it has high ΔE, η, and χ in DFT analysis.</p><p><strong>Conclusion: </strong>The novel-designed lead molecules demonstrate an enhanced pharmacokinetic profile, superior binding affinity, and minimal toxicity, based on computational study. These attributes make them promising candidates for further optimization as glucokinase activators.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}