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Molecular docking and dynamics analysis of selected phytocompounds against multi-targeted hepatocellular carcinoma. 部分植物化合物抗多靶点肝癌的分子对接及动力学分析。
IF 2.5
Drug Target Insights Pub Date : 2026-04-23 eCollection Date: 2026-01-01 DOI: 10.33393/dti.2026.3739
Narendran Chiterasu, Swarnalatha Yanamandala, Senthilkumar Chinnaiyan, Sivakumar Shanthirappan, Sidhika Kannan, Paul X Clinton, Karthick Vadivel, Kiruthika Alepalli Rangan, Suresh Babu Yashwanth
{"title":"Molecular docking and dynamics analysis of selected phytocompounds against multi-targeted hepatocellular carcinoma.","authors":"Narendran Chiterasu, Swarnalatha Yanamandala, Senthilkumar Chinnaiyan, Sivakumar Shanthirappan, Sidhika Kannan, Paul X Clinton, Karthick Vadivel, Kiruthika Alepalli Rangan, Suresh Babu Yashwanth","doi":"10.33393/dti.2026.3739","DOIUrl":"https://doi.org/10.33393/dti.2026.3739","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide, with a five-year survival rate of only 19%. Although Sorafenib is the primary systemic therapy, its limited efficacy and complex interactions with signaling pathways highlight the need for multi-target drugs.</p><p><strong>Methods: </strong>This study evaluates the anti-cancer properties of selected phytochemicals against six key HCC target proteins, utilizing sorafenib tosylate as a positive control. Molecular docking was performed to evaluate binding affinities and interactions, and ADME/T predictions were generated to estimate drug-like properties. The top-ranking candidates were further evaluated using 100-ns molecular dynamics simulations to analyze conformational stability, protein-ligand interactions, and residue mobility.</p><p><strong>Results: </strong>Silymarin (SA) emerged as the most effective compound, demonstrating greater predicted inhibitory activity than Sorafenib. SA showed high binding affinity for target proteins 6HH1 (-9.9 kcal/mol) and 1CM8 (-9.6 kcal/mol). Molecular dynamics simulations also revealed increased stability of the SA-protein complexes, particularly for the 1CM8-SA complex, which maintained high conformational stability. The root-mean-square deviation (RMSD) value was found to be around 2.1 Å, and the root-mean-square fluctuation (RMSF) values were below 3 Å, indicating lower protein flexibility compared to both the native and sorafenib-bound complexes.</p><p><strong>Conclusion: </strong>These computational findings provide a strong theoretical basis for Silymarin's efficacy as a highly potent, multi-targeted therapeutic agent against HCC. The improved stability and binding properties of Silymarin compared with Sorafenib provide a strong rationale for advancing this compound into preclinical and clinical studies.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"20 ","pages":"3-11"},"PeriodicalIF":2.5,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13107123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Alternative model organisms: growing popularity, and the challenges. 替代模式生物:日益流行和挑战。
IF 2.5
Drug Target Insights Pub Date : 2026-02-17 eCollection Date: 2026-01-01 DOI: 10.33393/dti.2026.3733
Vijay Kothari
{"title":"Alternative model organisms: growing popularity, and the challenges.","authors":"Vijay Kothari","doi":"10.33393/dti.2026.3733","DOIUrl":"https://doi.org/10.33393/dti.2026.3733","url":null,"abstract":"","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"20 ","pages":"1-2"},"PeriodicalIF":2.5,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12911325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antioxidant potential of a new macrocyclic bisbibenzyl and other compounds from Combretum molle: in vitro and docking analyses. Combretum molle中一种新的大环双苯和其他化合物的抗氧化潜力:体外和对接分析。
IF 2.5
Drug Target Insights Pub Date : 2025-12-18 eCollection Date: 2025-01-01 DOI: 10.33393/dti.2025.3631
Angele Fanta, Gaetan Bayiha Ba Njock, Amadou Dawe, Fawai Yakai, Jean Noël Nyemb, Herve Landry Ketsemen, Vincent Taira, Albert Wangso, Chantal Doudja, Dieudonne Emmanuel Pegnyemb, Benoit Loura
{"title":"Antioxidant potential of a new macrocyclic bisbibenzyl and other compounds from <i>Combretum molle</i>: <i>in vitro</i> and docking analyses.","authors":"Angele Fanta, Gaetan Bayiha Ba Njock, Amadou Dawe, Fawai Yakai, Jean Noël Nyemb, Herve Landry Ketsemen, Vincent Taira, Albert Wangso, Chantal Doudja, Dieudonne Emmanuel Pegnyemb, Benoit Loura","doi":"10.33393/dti.2025.3631","DOIUrl":"10.33393/dti.2025.3631","url":null,"abstract":"<p><strong>Introduction: </strong>Free radicals are key contributors to several diseases, including cancer, inflammation, pain, and neurodegenerative disorders such as Alzheimer's disease. Due to the limitations and adverse effects of synthetic antioxidants, naturally occurring phytochemicals offer safer, more sustainable alternatives. This study investigates the antioxidant potential of twigs of <i>Combretum molle</i> R. Br. ex G. Don through integrated experimental and computational approaches.</p><p><strong>Methods: </strong>Compounds were isolated using chromatographic methods, and their structures established by 1D- and 2D-NMR, HR-ESI-MS, and comparison with reported data. Antioxidant activity was assessed through DPPH radical scavenging and FRAP assays, while molecular docking against xanthine oxidase (PDB: 1FIQ) explored possible mechanisms beyond direct radical scavenging.</p><p><strong>Results: </strong>A new macrocyclic bisbibenzyl derivative, combrebisbibenzyl A (<b>1</b>), was identified along with corosolic acid (<b>2</b>), maslinic acid (<b>3</b>), a mixture of asiatic acid (<b>4</b>) and arjunolic acid (<b>5</b>), combregenin (<b>6</b>), and β-sitosterol glucoside (<b>7</b>). The MeOH extract and EtOAc fraction showed notable DPPH scavenging activity (IC₅₀ = 170.21 and 197.41 μg/mL) and strong reducing power (65.04 ± 1.07 and 67.42 ± 0.82 mM Vit C/g). Among the isolated compounds, combrebisbibenzyl A (<b>1</b>) displayed the strongest radical scavenging effect (IC₅₀ = 175.64 μg/mL) and high reducing capacity (57.46 ± 0.42 mM Vit C/g). Docking indicated favorable interactions for all compounds, with combrebisbibenzyl A (<b>1</b>) showing the highest affinity (-9.1 kcal/mol), outperforming salicylate (-7.7 kcal/mol).</p><p><strong>Conclusion: </strong>These findings support the traditional use of <i>C. molle</i> and highlight combrebisbibenzyl A (<b>1</b>) as a promising natural antioxidant with multi-mechanistic potential.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"19 ","pages":"108-115"},"PeriodicalIF":2.5,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12723388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ravulizumab in treatment-naïve patients with atypical hemolytic uremic syndrome: a real-world case series. Ravulizumab治疗treatment-naïve非典型溶血性尿毒症综合征患者:真实世界病例系列
IF 2.5
Drug Target Insights Pub Date : 2025-12-09 eCollection Date: 2025-01-01 DOI: 10.33393/dti.2025.3616
Sorrentino Livia Maria, Candida Iacuzzo, Raffaela Sciri, Miriam Zacchia, Mariarosaria Iannuzzi, Paola Marotta, Piercarla Vitale, Chiara Taglioni, Floriana Secondulfo, Daniela Palazzetti, Rocco Baccaro
{"title":"Ravulizumab in treatment-naïve patients with atypical hemolytic uremic syndrome: a real-world case series.","authors":"Sorrentino Livia Maria, Candida Iacuzzo, Raffaela Sciri, Miriam Zacchia, Mariarosaria Iannuzzi, Paola Marotta, Piercarla Vitale, Chiara Taglioni, Floriana Secondulfo, Daniela Palazzetti, Rocco Baccaro","doi":"10.33393/dti.2025.3616","DOIUrl":"10.33393/dti.2025.3616","url":null,"abstract":"<p><strong>Introduction: </strong>Atypical hemolytic uremic syndrome (aHUS) is a potentially life-threatening condition associated with poor clinical outcomes if not treated adequately. Eculizumab has become the standard of care, whereas ravulizumab, a second-generation, high-affinity complement C5 inhibitor, demonstrates comparable efficacy in improving renal function, hematological markers, and dialysis rates. In addition, ravulizumab offers practical advantages, including a longer dosing interval and immediate, complete, and sustained inhibition of free C5, making it a valuable therapeutic option.</p><p><strong>Methods: </strong>Given the limited real-world experience with ravulizumab, we present a case series of six treatment-naïve aHUS patients who received ravulizumab as first-line therapy.</p><p><strong>Results: </strong>These cases include one pregnancy-related aHUS, one postpartum case, one related to a urinary tract infection, one associated with hypertension, one with a pneumonia-related trigger, and one kidney transplant patient with a prior verotoxin-producing <i>E. coli</i> infection. Altogether, these cases illustrate the challenges in diagnosing aHUS. The choice to administer ravulizumab as first-line treatment was sometimes made in the presence of a clear clinical suspicion, even when not all minor criteria seemed to confirm the diagnosis. In most patients, renal function improved rapidly after ravulizumab administration, followed by recovery of hematological parameters, which were stable in the longer term. As improvements remained sustained over time, the possibility of discontinuing ravulizumab can be evaluated on a case-by-case basis.</p><p><strong>Conclusion: </strong>These cases highlight the importance of early diagnosis, prompt intervention, and multidisciplinary care in managing aHUS. Ravulizumab as first-line therapy proved effective and well-tolerated, with sustained clinical improvements observed across diverse real-world scenarios.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"19 ","pages":"99-107"},"PeriodicalIF":2.5,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12687736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Co-occurrence of genes encoding carbapenem resistance and aminoglycoside resistance in clinical isolates of Enterobacterales. 肠杆菌临床分离株碳青霉烯类耐药基因与氨基糖苷类耐药基因共现。
IF 2.5
Drug Target Insights Pub Date : 2025-10-27 eCollection Date: 2025-01-01 DOI: 10.33393/dti.2025.3592
Shradha Smriti, Gaurav Verma, Sujit Pradhan, Nipa Singh, Subhra Snigdha Panda, Ipsa Mohapatra, Dipti Pattnaik, Rajesh Kumar Dash, Liza Das
{"title":"Co-occurrence of genes encoding carbapenem resistance and aminoglycoside resistance in clinical isolates of Enterobacterales.","authors":"Shradha Smriti, Gaurav Verma, Sujit Pradhan, Nipa Singh, Subhra Snigdha Panda, Ipsa Mohapatra, Dipti Pattnaik, Rajesh Kumar Dash, Liza Das","doi":"10.33393/dti.2025.3592","DOIUrl":"10.33393/dti.2025.3592","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to detect the co-occurrence of carbapenem resistance genes along with aminoglycoside-modifying enzyme (AME) genes in clinical <i>Enterobacterales</i> isolates to understand the distribution of multiple resistance genes among clinical isolates.</p><p><strong>Methods: </strong>This prospective study was conducted for six months (November 2024 to April 2025) in the department of microbiology of a tertiary care hospital. A total of 30 blood culture isolates were identified as resistant to both carbapenem and aminoglycoside antibiotics using the automated VITEK 2 compact system. The genes responsible for carbapenem resistance (<i>bla<sub>NDM</sub></i> , <i>bla<sub>OXA-48</sub></i> , <i>bla<sub>KPC</sub></i> , <i>bla<sub>IMP</sub></i> , and <i>bla<sub>VIM</sub></i> ) were detected by multiplex real-time PCR, and the aminoglycoside-modifying enzyme genes [APH(3')-Ia, APH(2\")-Ib, AAC(3)-IIc, AAC(6')-Ib, and ANT(3\")-I] were detected by the conventional polymerase chain reaction method. All the clinical data, patient demographics, and molecular findings were entered in an MS Excel spreadsheet version 14.0.4734.1000 and analyzed using GraphPad/PRISM software version 10.5.0.</p><p><strong>Results: </strong>Of the 30 <i>Enterobacterales</i> isolates, <i>Klebsiella pneumoniae</i> was the most common isolate (66.7%). Molecular detection revealed <i>bla<sub>NDM</sub></i> in 40% isolates and <i>bla<sub>OXA48</sub></i> in 10% isolates. The majority of the AME genes were in combination. The most common combination of the AME gene was AAC(6')-Ib+ AAC(3)-IIc+ ANT(3\")-I + APH(3')-I detected in 4 (13.3%) isolates. The most common combination of carbapenem and aminoglycoside resistant genes was <i>bla<sub>NDM</sub></i> + <i>bla<sub>OXA48</sub></i> + AAC(6')-Ib+ AAC(3)-IIc+ ANT(3\")-I+ APH(3')-I (13.3%). The <i>bla<sub>OXA-48</sub></i> gene had a statistically significant association with AAC(6')-Ib, ANT(3\")-I, and APH(3')-I (p <0.05).</p><p><strong>Conclusion: </strong>The Co-occurence of carbapenem resistance and aminoglycoside-modifying enzyme genes in clinical <i>Enterobacterales</i> isolates limits the therapeutic option.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"19 ","pages":"91-98"},"PeriodicalIF":2.5,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12569621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145408497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integrated in vitro, microarray, and network pharmacology analysis reveals the multi-target anti-diabetic potential of Vigna unguiculata. 综合体外、微阵列和网络药理学分析揭示了马蹄莲的多靶点抗糖尿病潜力。
IF 2.5
Drug Target Insights Pub Date : 2025-08-21 eCollection Date: 2025-01-01 DOI: 10.33393/dti.2025.3495
Haseeba Sardar, Fatima Noor, Syed Muhammad Mukarram Shah, Ashraf Ullah Khan, Jamelah S Al-Otaibi, Fazal Hadi, Maria Daglia, Haroon Khan
{"title":"Integrated <i>in vitro</i>, microarray, and network pharmacology analysis reveals the multi-target anti-diabetic potential of <i>Vigna unguiculata</i>.","authors":"Haseeba Sardar, Fatima Noor, Syed Muhammad Mukarram Shah, Ashraf Ullah Khan, Jamelah S Al-Otaibi, Fazal Hadi, Maria Daglia, Haroon Khan","doi":"10.33393/dti.2025.3495","DOIUrl":"10.33393/dti.2025.3495","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetes mellitus (DM), particularly type 2 DM (T2DM), is a chronic metabolic disorder requiring novel therapeutic approaches as the available therapies are not meeting the current challenges. This study investigates the anti-diabetic potential of Vigna unguiculata using a network pharmacology approach, supported by <i>in vitro</i> and <i>in silico</i> analyses.</p><p><strong>Methods: </strong>The plant was collected from Khyber Pakhtunkhwa, Pakistan, and subjected to hydroalcoholic extraction and fractionation. <i>In vitro</i> assays included α-amylase, α-glucosidase, and aldose reductase. Target prediction using STITCH and SwissTargetPrediction identified 88 common genes linked to T2DM. Protein-protein interaction (PPI) network analysis highlighted key genes like EGFR, PTGS2, and TLR4 as central nodes in diabetes-related pathways. Molecular docking was used to study the binding affinities of compounds.</p><p><strong>Results: </strong>IC50 values were determined using IBM SPSS Statistics 21 software. The data underwent analysis using one-way ANOVA followed by Dunnett's multiple comparison test. Significance value was determined at *p   0.05, **p   0.01 and ***p   0.001. In-vitro assays demonstrated significant α-amylase, α-glucosidase, and aldose reductase inhibitory activities. Phytochemical screening identified several bioactive compounds. Functional annotation and KEGG pathway analysis confirmed these genes' roles in crucial metabolic pathways. Virtual screening revealed strong binding affinities of compounds like Stigmasterol, Luteoline, and Quercetin with GSK3B, PTGS2, and TLR4. The Molecular Dynamics (MD) simulation, binding free energy calculations (MM-PBSA and MM-GBSA), confirmed the results of Virtual screening.</p><p><strong>Conclusion: </strong>In short, these findings underscore <i>V. unguiculata</i> as a promising source for anti-diabetic agents, supporting further clinical trials for T2DM management.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"19 ","pages":"71-90"},"PeriodicalIF":2.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12371541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Bushenhuoxue formula improves prothrombotic state in recurrent spontaneous abortion: network pharmacology and experimental validation. 补肾活血方改善复发性自然流产血栓形成前状态:网络药理学及实验验证。
IF 2.5
Drug Target Insights Pub Date : 2025-08-19 eCollection Date: 2025-01-01 DOI: 10.33393/dti.2025.3562
Xuan Yang, Shulan Su, Lijing Liu, Pan Liu, Maoqing Lu, Yinuo Wei, Yaqiong Gao
{"title":"The Bushenhuoxue formula improves prothrombotic state in recurrent spontaneous abortion: network pharmacology and experimental validation.","authors":"Xuan Yang, Shulan Su, Lijing Liu, Pan Liu, Maoqing Lu, Yinuo Wei, Yaqiong Gao","doi":"10.33393/dti.2025.3562","DOIUrl":"10.33393/dti.2025.3562","url":null,"abstract":"<p><strong>Introduction: </strong>Bushenhuoxue formula is a traditional Chinese medicine formula with relatively safe clinical effects, but its mechanism in recurrent spontaneous abortion (RSA) is still unclear. Our present study used Network pharmacology an experimental validation to discuss how Bushenhuoxue formula improves prethrombotic state in RSA.</p><p><strong>Materials and methods: </strong>The active ingredients of Bushenhuoxue formula (Drug) were acquired from our previous study. The putative targets of ZYP relevant to AS were obtained from TCMSP, Swiss Target Prediction, STITCH, DisGeNET, and Gene Cards databases. Protein-protein interactions (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted using the Cytoscape software. Furthermore, <i>in vivo</i> experiments were carried out for target validation in BALB/c mice, collecting placental tissue from different groups, the cell apoptosis by TUNEL assay; the pathology by HE staining; relative mRNA expression by qRT-PCR assay; relative protein expression by IHC and WB assay.</p><p><strong>Results: </strong>Animal experiments, compared with the NC group, the AT-III, PROG, HCG, APC and t-PA concentrations were significantly depressed (P˂0.05, respectively), Apoptosis cell numbers were significantly up-regulated with PI3K/AKT/HIF-1<i>α</i> VEGF significantly depressing (P˂0.001, respectively). With Bushenhuoxue formula supplement, AT-III, PROG, HCG, APC and t-PA concentrations were significantly improved in RSA model mice; and improved pathological changes and apoptosis cell number in placenta tissues (P˂0.05, respectively). However, with LY294002 supplement, the drug treatment effects were disappeared.</p><p><strong>Conclusion: </strong>Bushenhuoxue formula improves prethrombotic state in RSA <i>via</i> stimulating PI3K/AKT/HIF-1α/VEGF pathway <i>in vivo.</i></p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"19 ","pages":"59-70"},"PeriodicalIF":2.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integrative in silico and Petra/Osiris/Molinspiration (POM) analysis of baicalein: identification of therapeutically relevant pharmacophores against keloid pathology. 黄芩苷的综合硅和Petra/Osiris/Molinspiration (POM)分析:对瘢痕疙瘩病理治疗相关药效团的鉴定。
IF 2
Drug Target Insights Pub Date : 2025-07-16 eCollection Date: 2025-01-01 DOI: 10.33393/dti.2025.3574
Abhay P Mishra, Anothai Tangsumranjit, Manisha Nigam, Harish Chandra, Faisal A Almalki, Taibi B Hadda, Neti Waranuch
{"title":"Integrative <i>in silico</i> and Petra/Osiris/Molinspiration (POM) analysis of baicalein: identification of therapeutically relevant pharmacophores against keloid pathology.","authors":"Abhay P Mishra, Anothai Tangsumranjit, Manisha Nigam, Harish Chandra, Faisal A Almalki, Taibi B Hadda, Neti Waranuch","doi":"10.33393/dti.2025.3574","DOIUrl":"10.33393/dti.2025.3574","url":null,"abstract":"<p><strong>Introduction: </strong>Keloid scars are a kind of skin disorder in which the scar grows beyond the boundaries of the original wound. Baicalein, a flavonoid, may treat keloids by targeting fibrosis, inflammation, and possible viral factors.</p><p><strong>Methods: </strong>In silico studies were conducted to evaluate the potential anti-keloid effects of baicalein by predicting its interactions with three key proteins of the transforming growth factor-β (TGF-β) family (PDB IDs: 1VJY, 3TZM, and 7DV6). POM analysis was also used to understand the conditions that could enhance baicalein's efficacy.</p><p><strong>Results: </strong>The results indicated that baicalein binds effectively to TGF-β family proteins via hydrogen bonds, showing strong affinities (1VJY: -9.9 kcal/mol, 3TZM and 7DV6: -9.3 kcal/mol), indicating its potential as a TGF-β receptor ligand. Osiris analysis gave a drug score of 75% for baicalein, while Molinspiration indicated good bioavailability with a cLogP of 2.84. Atomic charge distribution and pharmacophore site mapping through POM analysis indicate that baicalein exhibits an antiviral pharmacophoric moiety akin to known antiviral agents. This indicates that baicalein may act as a pro-drug, undergoing metabolic transformation to form a bis-bidentate ligand. Such ligands are crucial for forming bimetallic complexes that can function as efficient biocatalysts against various biological targets.</p><p><strong>Conclusion: </strong>In-silico analysis suggests that baicalein may influence TGF-β receptors and exhibit anti-keloid activity. Additionally, POM analysis recommends that baicalein may serve as a lead compound with the potential to modulate TGF-β signalling and exhibit antiviral properties, indicating it as a dual-action agent against keloids and viral infections.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"19 ","pages":"49-58"},"PeriodicalIF":2.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Anti-Inflammatory and Regenerative Properties of Herbal Extracts: Wound Management in Equine Models. 草药提取物的抗炎和再生特性:马模型的伤口管理。
IF 2
Drug Target Insights Pub Date : 2025-05-29 eCollection Date: 2025-01-01 DOI: 10.33393/dti.2025.3499
Gustavo W Fehrenbach, Katie Sheils, Mariana J Silva, Jessica Walshe, Lena Madden, Ian Major, Niall Burke, Tim Yeomans, Emanuele Rezoagli, Emma J Murphy
{"title":"Anti-Inflammatory and Regenerative Properties of Herbal Extracts: Wound Management in Equine Models.","authors":"Gustavo W Fehrenbach, Katie Sheils, Mariana J Silva, Jessica Walshe, Lena Madden, Ian Major, Niall Burke, Tim Yeomans, Emanuele Rezoagli, Emma J Murphy","doi":"10.33393/dti.2025.3499","DOIUrl":"10.33393/dti.2025.3499","url":null,"abstract":"<p><strong>Introduction: </strong>Wound management presents significant challenges, requiring effective treatments. Herbal extracts have been traditionally used to support healing due to their anti-inflammatory, antimicrobial, and cell-regenerative properties.</p><p><strong>Methods: </strong>This study aimed to evaluate the therapeutic efficacy of Pau D'Arco (<i>Tabebuia</i>), Yarrow (<i>Achillea millefolium</i>), Gotu Kola (<i>Centella asiatica</i>), Figwort (<i>Scrophularia nodosa</i>), and Broadleaf (<i>Plantago major</i>) extracts, both individually and combined, on wound healing <i>in vitro</i> and <i>in vivo</i> in equine models. <i>In vitro</i> tests using human macrophages and keratinocyte cell lines to assess cellular responses such as cytokine secretion and phagocytic activity under simulated inflammatory conditions. Additionally, pilot case studies on equines with open wounds provided practical insights into the extracts' healing capabilities.</p><p><strong>Results: </strong>MTT assay was used to assess cytotoxicity. The extracts did not significantly affect the viability of HaCaT or THP-1 cells. The herbal extracts reduced IL-8 levels and increased phagocytic activity in macrophages, indicating an ability to modulate inflammatory responses. <i>In vivo</i>, the extracts were well tolerated and associated with supported healing in equines. These effects were suggested to be attributed to the synergistic actions of the herbal components.</p><p><strong>Conclusion: </strong>These findings suggest that the herbal extracts may be useful for supporting wound healing. Their natural anti-inflammatory and healing properties could provide an additional option alongside traditional wound management approaches.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"19 ","pages":"41-48"},"PeriodicalIF":2.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12124212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Establishment and evaluation of a naked-eye diagnostic assay for tuberculosis utilizing reverse isothermal amplification-assisted CRISPR-Cas in resource-limited settings. 在资源有限的环境下,利用逆温扩增辅助CRISPR-Cas建立和评估裸眼结核病诊断方法。
IF 2
Drug Target Insights Pub Date : 2025-05-09 eCollection Date: 2025-01-01 DOI: 10.33393/dti.2025.3304
Ankush Kaushik, Jitendra Singh, Zeeshan Fatima, Saif Hameed
{"title":"Establishment and evaluation of a naked-eye diagnostic assay for tuberculosis utilizing reverse isothermal amplification-assisted CRISPR-Cas in resource-limited settings.","authors":"Ankush Kaushik, Jitendra Singh, Zeeshan Fatima, Saif Hameed","doi":"10.33393/dti.2025.3304","DOIUrl":"https://doi.org/10.33393/dti.2025.3304","url":null,"abstract":"<p><strong>Introduction: </strong>The current scenario of tuberculosis (TB) caused by <i>Mycobacterium tuberculosis</i> (MTB) has presented an almost insurmountable challenge to hospitals with high patient numbers. Delayed diagnosis of TB is a major hurdle in preventing the employment of efficient therapeutics, leading to the development of drug resistance. Hence, an easily accessible diagnostic method, particularly for resource for resource-limited settings, is pertinent for the rapid identification of MTB-infected patients. In pursuit of developing such an assay, the present study offers a CLAP-TB (CRISPR-Cas coupled RT-LAMP Amplification Protocol for Tuberculosis) assay, which will allow us to diagnose TB rapidly and visually.</p><p><strong>Methods and results: </strong>Herein, the visual MTB detection consists of a method utilizing 232 different samples (sputum, urine, serum) from 82 patients for reverse transcription loop-mediated isothermal amplification (RT-LAMP). Additionally, the assay also utilizes the integration of a CRISPR-Cas12-based system using different guide RNAs of <i>IS6110</i> and an internal control <i>POP7</i> (human RNase P) genes along with visual detection via lateral flow readout-based dipsticks with the unaided eye (~134 min). Overall, the limit of detection for CLAP-TB assay was up to 1 ag of RNA, while the clinical sensitivity and specificity were 98.27% and 100%, respectively, on the pilot scale.</p><p><strong>Conclusion: </strong>Together, our CLAP-TB assay offers proof of concept for a rapid, sensitive, and specific method with the minimum technical expertise required for TB diagnosis in developing and resource-limited settings.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"19 ","pages":"31-40"},"PeriodicalIF":2.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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