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

{"title":"Naringenin: A Promising Immunomodulator for Anti-inflammatory, Neuroprotective and Anti-cancer Applications.","authors":"Sarita Solanki, Himangi Vig, Nidhi Khatri, Bhanu Pratap Singh, Mohammad Shahid Khan, Manish Devgun, Pranay Wal, Ankita Wal","doi":"10.2174/0118715230320007240708074939","DOIUrl":"10.2174/0118715230320007240708074939","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory, immune, and neurodegenerative diseases constitute a category of persistent and debilitating conditions affecting millions worldwide, with intertwined pathophysiological pathways. Recent research has spotlighted naturally occurring compounds like naringenin for potential therapeutic applications across multiple ailments.</p><p><strong>Objectives: </strong>This review offers an encompassing exploration of naringenin's anti-inflammatory, immune-protective, and neuroprotective mechanisms, elucidating its pharmacological targets, signal transduction pathways, safety profile, and insights from clinical investigations.</p><p><strong>Methods: </strong>Data for this review were amassed through the scrutiny of various published studies <i>via</i> search engines such as PubMed and Google Scholar. Content from reputable publishers including Bentham Science, Taylor and Francis, Nature, PLOS ONE, among others, was referenced.</p><p><strong>Results: </strong>Naringenin exhibits substantial anti-inflammatory effects by restraining the NF-κB signaling pathway. It activates Nrf2, renowned for its anti-inflammatory properties, inducing the release of hemeoxynase-1 by macrophages. Furthermore, naringenin treatment downregulates the expression of Th1 cytokines and inflammatory mediators. It also impedes xanthine oxidase, counteracts reactive oxygen species (ROS), scavenges superoxide radicals, mitigates the accessibility of oxygen-induced K+ erythrocytes, and reduces lipid peroxidation. Naringenin's antioxidant prowess holds promise for addressing neurological conditions.</p><p><strong>Conclusion: </strong>Extensive research has been undertaken to establish the anti-inflammatory, immunomodulatory, and neuroprotective attributes of naringenin across various medical domains, lending credence to its pharmacological utility. The principal obstacle to naringenin's adoption as a therapeutic agent remains the dearth of in vivo data. Efforts should focus on rendering naringenin delivery patient-friendly, economically viable, and technologically advanced.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":"1-25"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794486","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 <i>Kappaphycus alvarezii</i> in High Cholesterol-induced Zebrafish Larvae: Revealing Cardiovascular Potential.","authors":"Rabika Ramalingam, Kaliyamurthi Venkatachalam, Ambika Binesh","doi":"10.2174/0118715230342356250611114954","DOIUrl":"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. UVvisible, 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 highcholesterol 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><i>Kappaphycus alvarezii</i> 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":"234-241"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","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 Paraiso, Jaciara Neves Sousa, Joao Marcus Oliveira Andrade, Eloa Mangabeira Santos, Debora de Farias Lelis, Charles Santos Da Costa, Jones Bernardes Graceli, Bruna Kaicy Barbosa, Lucyana Conceicao Farias, Alfredo Mauricio Batista de Paula, Andre Luiz Sena Guimaraes, Daniele Teixeira Alves, Maik Gollasch, Robson Augusto Souza Santos, Sergio Henrique Sousa Santos","doi":"10.2174/0118715230367867250613134043","DOIUrl":"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 <i>in silico</i> 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":"257-268"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","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":"Toxicity and Anti-inflammatory Effects of <i>Eleutherine bulbosa</i> (Miller) Urb, Ethanolic Extract, in Zebrafish <i>(Danio rerio)</i>.","authors":"Dionisia P Ferreira, Fabrício H Holanda, Swanny F Borges, Ryan da S Ramos, Victoria Mae T Shinkai, Gisele C de Souza, Jose Carlos T Carvalho, Raphael S Pimenta, Jose Luiz M do Nascimento, Irlon M Ferreira","doi":"10.2174/0118715230352701241130053455","DOIUrl":"10.2174/0118715230352701241130053455","url":null,"abstract":"<p><strong>Introduction: </strong>Eleutherine bulbosa (Miller) Urb, popularly known as \"marupazinho\", is frequently used in traditional medicine for treating various diseases, including hypertension, ulcers, constipation, and intestinal infection. However, there is little scientific knowledge available regarding the pharmacological effects of this species. Thus in vivo and in silico phytochemical studies are required to establish whether this plant has these effects. Further tests were necessary to evaluate the pharmacological activity of the compounds found in this plant, and demonstrate results related to the anti-inflammatory process, which will serve as the basis for future research in this area.</p><p><strong>Methods: </strong>Therefore, our study aimed to determine the acute toxicity levels of the hexanoic fraction of the ethanolic extract of Eleutherine bulbosa (referred to as ExtHF) using adult zebrafish, with the determination of the LD50, behavioral and histopathological evaluations, as well as the anti-inflammatory potential of ExtHF, at different doses, in abdominal edema induced by carrageenan. The acute toxicity study and histopathological analysis in zebrafish showed that ExtHF has a high toxic potential, with an LD50 of 346.74 mg/kg. However, ExtHF showed an anti-inflammatory effect by inhibiting abdominal edema at all doses tested.</p><p><strong>Results: </strong>The inhibition rate of 66.2% and 62.4%, respectively, was observed with the 2.5 mg/kg dose, respectively, indicating that ExtHF is safe in terms of acute toxicity based on behavioral changes, mortality rate, and histopathological examination. Therefore, ExtHF has an acceptable level of safety for acute toxicity, defined by the analysis of behavioral changes, mortality, and histopathology, showing a significant anti-inflammatory effect in zebrafish at all doses, showing that ExtHF was very efficient in preventing the formation of edema, in addition, it was also revealed that ExtHF has a great effect in reversing the edema which is already installed.</p><p><strong>Conclusion: </strong>Molecular docking studies revealed that the eleutherol molecule isolated from E. bulbosa has a dual inhibition profile against cyclooxygenase-1 and 2.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":"199-214"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934153","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":"Molecular Docking, Pharmacophore Modeling and ADMET Prediction of Novel Heterocyclic Leads as Glucokinase Activators.","authors":"Anuradha Mehra, Amit Mittal, Shivangi Singh","doi":"10.2174/0118715230325278240821053346","DOIUrl":"10.2174/0118715230325278240821053346","url":null,"abstract":"<p><strong>Background: </strong>A pivotal impetus has driven the development of numerous small molecules aiming to improve therapeutic strategies for type 2 diabetes. Glucokinase (GK) activation has been offered a new realm of therapeutic antidiabetic activity with novel heterocyclic derivatives. In the context of antidiabetic drug design, GK is an interesting and newly validated target. A key enzyme needed for blood glucose homeostasis is Glucokinase, which is dysfunctional in individuals with type 2 diabetes. Heterocyclic derivatives are utilized in this innovative approach to activate GK enzymes as medicinal agents that will significantly improve type 2 diabetes management.</p><p><strong>Objectives: </strong>To address type 2 diabetes, as well as minimize unwanted side effects, this research endeavor aimed to develop activators of glucokinase.</p><p><strong>Methods: </strong>A rigorous scrutiny was conducted of the Maybridge online repository, which houses a formidable collection of 53,000 lead compounds. A collection of 125 compounds that contain the thiazolidinedione core was selected from this extensive collection. The structures were generated using ChemDraw 2D, stabilized conformation with ChemBioDraw Ultra, and docked using Auto Dock Vina 1.5.6 in this methodology. In addition, log P was predicted online using the Swiss ADME algorithm. The PKCSM software was used to predict the toxicity of the leading compounds.</p><p><strong>Results: </strong>The highest binding affinity was found for AS72 and AS108 to GK receptors. GI absorption and excretion of these compounds were efficient due to Lipinski's Rule of Five compliance. When compared with the standard drugs Dorzagliatin (GKA) and MRK (co-crystallized ligand), these substances demonstrated a notable lack of AMES toxicity, skin sensitization, and hepatotoxicity.</p><p><strong>Conclusion: </strong>In recent studies, lead molecules that possess enhanced pharmacokinetic profiles, increased binding affinity, and lower toxicity were developed to act as glucokinase activators.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":"57-74"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335936","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":"Discovery and Chemical Exploration of Spiro[Benzofuran-3,3'-Pyrroles] Derivatives as Innovative FLT3 Inhibitors for Targeting Acute Myeloid Leukemia.","authors":"Mohammed M Al-Mahadeen, Areej M Jaber, Jalal A Zahra, Belal O Al-Najjar, Mustafa M El-Abadelah, Monther A Khanfar","doi":"10.2174/0118715230343474241009112335","DOIUrl":"10.2174/0118715230343474241009112335","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed at the synthesis of several spiro[benzofuran-3,3'-pyrroles] derivatives by a three-component reaction conducted by mixing DMAD, <i>N</i>-bridgehead heterocycles, and benzofuran-2,3-diones in dichloromethane at room temperature for 24 h. Moreover, <i>in vitro</i> evaluation of their cytotoxicity affinities against FMS-like tyrosine kinase 3 was carried out.</p><p><strong>Objectives: </strong>The objective of this study was to use a one-pot, three-component reaction to synthesize a novel set of spiro[benzofuran-3,3'-pyrroles] derivatives.</p><p><strong>Methods: </strong>A novel set of spiro[benzofuran-3,3'-pyrroles] ((11-13)a-e) was synthesized by a one-pot three-component reaction involving dimethyl acetylenedicarboxylate, <i>N</i>-bridgehead heterocycles and benzofuran-2,3-diones in dichloromethane at room temperature for 24 h. The compounds were analyzed using NMR ¹H, ¹³C, 2D-NMR (COSY, HMQC, HMBC), and HRMS. Docking simulations were conducted to elucidate the anticancer activity of synthesized compounds on FLT3 protein, with Gilteritinib as a reference for comparison.</p><p><strong>Results: </strong>This study demonstrated the successful design, synthesis, and biological evaluation of spiro[benzofuran-3,3'-pyrroles] derivatives as FLT3 inhibitors for AML treatment. The synthesized compounds demonstrated promising binding affinities and significant inhibitory activity against FLT3 kinase. The inhibitors (11a, 11b, 11c, 12d, and 12e) exhibited excellent selectivity profiles against FLT3. Particularly, compound 12e showed strong binding affinity and potent inhibitory activity (IC₅₀ = 2.5 μM).</p><p><strong>Conclusion: </strong>Fifteen new synthetic spiro[benzofuran-3,3'-pyrroles] were prepared, characterized, and evaluated for cytotoxicity affinities against FMS-like tyrosine kinase 3. Compound 12e showed strong binding affinity and potent inhibitory activity (IC₅₀ = 2.5 μM), making it a promising candidate for further development as a therapeutic option for AML treatment. These findings lay the groundwork for further optimization and development of spiro[benzofuran-3,3'-pyrroles] derivatives as potential therapeutics for AML treatment. Further studies are needed to explore their efficacy and safety profiles in preclinical and clinical settings.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":"127-138"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796772","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 <i>in vitro</i> Study.","authors":"Saravanan Sampoornam Pape Reddy, Delfin Lovelina Francis, Soumi Mondal, Manish Rathi, Neelima Katti, Sukhbir Singh Chopra","doi":"10.2174/0118715230384352250526103643","DOIUrl":"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 cytotoxic and anti-inflammatory properties of a novel essential oil compound containing 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 cytotoxicity 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 using ELISA, and COX-2 inhibition assay was performed.</p><p><strong>Results: </strong>Cytotoxicity of the test compound was nearly absent. TNF-α levels decreased in positive control (2.81 pg/ml) and test samples (1.30 pg/ml) compared to control (22.04 pg/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-silvercontaining compounds as a medication material in preventing gingivitis. The cytotoxicity 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":"269-277"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","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":"Optimization and <i>In-Vitro</i> Characterization of Tetrahydrocurcumin Loaded Niosome for Psoriasis Management.","authors":"Akash Garg, Chetan Singh Chauhan, Rohitas Deshmukh, Rutvi Agrawal","doi":"10.2174/0118715230385381250807024537","DOIUrl":"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>Methods: </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":"278-292"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","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":"Leveraging Underutilized Sri Lankan Fruits in the Fight against Autoimmune Disorders.","authors":"Manamendra Patabandige Theja Virajini, Mithila Dulanjalee Bandara, Prasad Tharanga Jayasooriya, Kalpa Wishvajith Samarakoon, Anchala Ishani Kuruppu","doi":"10.2174/0118715230353359241211215415","DOIUrl":"10.2174/0118715230353359241211215415","url":null,"abstract":"<p><p>The potential of underutilized plant species to improve food security, health, economic output, and the environment has not been fully realized. Sri Lanka an island on the Indian Ocean is home to numerous plant species with significant medicinal potential, including many underutilized plants that could help meet the growing demand for food, energy, medicines, and industrial resources. Globally, there are over a thousand known and unknown phytochemicals derived from plants. Although these compounds are primarily produced by plants for self-defence, in vitro and in vivo studies have demonstrated their anti-inflammatory properties. Recent research indicates that several phytochemicals can also protect humans from disease by regulating key inflammatory pathways, such as NF-κB, MAPK, JAK/STAT and Nrf-2, which are involved in autoimmune diseases. Thus, these bioactive compounds are vital for managing managing immune related conditions. This review will explore underutilized fruit crops from Sri Lanka that could be used against inflammation, including autoimmune diseases.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":"149-166"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019592","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":"10.2174/0118715230352441250309014403","url":null,"abstract":"<p><strong>Background: </strong>The presence of insufficient insulin signaling in type 2 diabetes arises due to either insulin resistance or impaired insulin secretion, ultimately leading 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. Notably, 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>Objectives: </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 compounds. 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 compounds 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 sensitization, 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":"179-198"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","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}