Aspects of molecular medicine最新文献

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In silico identification of potential HDAC3 inhibitors through machine learning, molecular docking, and molecular dynamics simulations for drug repurposing 通过机器学习、分子对接和药物再利用的分子动力学模拟,在计算机上识别潜在的HDAC3抑制剂
Aspects of molecular medicine Pub Date : 2025-12-01 Epub Date: 2025-06-18 DOI: 10.1016/j.amolm.2025.100092
Damilare P. Dosunmu , Rachael Oluwakamiye Abolade , Mujeebat Bashiru , Adedoyin John-Joy Owolade , Muyiwa Kolawole Samuel , Ebunoluwa Omorilewa Boluwatife , Ayomadewa Mercy Olatunya , Precious O. Aribisala , Samuel Aduramurewa Osunnaya , Micheal Abimbola Oladosu , Ebenezer Ayomide Oni , Damilola Samuel Bodun
{"title":"In silico identification of potential HDAC3 inhibitors through machine learning, molecular docking, and molecular dynamics simulations for drug repurposing","authors":"Damilare P. Dosunmu ,&nbsp;Rachael Oluwakamiye Abolade ,&nbsp;Mujeebat Bashiru ,&nbsp;Adedoyin John-Joy Owolade ,&nbsp;Muyiwa Kolawole Samuel ,&nbsp;Ebunoluwa Omorilewa Boluwatife ,&nbsp;Ayomadewa Mercy Olatunya ,&nbsp;Precious O. Aribisala ,&nbsp;Samuel Aduramurewa Osunnaya ,&nbsp;Micheal Abimbola Oladosu ,&nbsp;Ebenezer Ayomide Oni ,&nbsp;Damilola Samuel Bodun","doi":"10.1016/j.amolm.2025.100092","DOIUrl":"10.1016/j.amolm.2025.100092","url":null,"abstract":"<div><h3>Background</h3><div>Histone Deacetylase 3 (HDAC3) is an epigenetic enzyme that controls cell cycle progression, apoptosis, and gene expression. Overexpression of HDAC3 has been shown to be a potential contributing factor to the development and spread of breast cancer, and it has recently been identified as a promising target in breast cancer. As a result, repurposing currently approved drugs as novel HDAC3 inhibitors may reduce the labor-intensive and time-consuming process of developing new molecules.</div></div><div><h3>Materials and methods</h3><div>We sourced 4288 compounds from the ZINC15-approved drugs. We then employed both virtual and structure-based screening to identify and repurpose current drugs as selective inhibitors against the HDAC3 target protein. MD simulation was performed to assess the dynamic behavior and stability of the top ligand complexes for 100 ns.</div></div><div><h3>Results</h3><div>This computational screening obtained the top five compounds with docking scores of <span><math><mrow><mo>−</mo></mrow></math></span> 10.96, <span><math><mrow><mo>−</mo></mrow></math></span> 10.32, <span><math><mrow><mo>−</mo></mrow></math></span> 9.83, <span><math><mrow><mo>−</mo></mrow></math></span> 9.83, and <span><math><mrow><mo>−</mo></mrow></math></span> 8.81 kcal/mol, respectively, in comparison with the reference ligand, BG45 (−4.18 kcal/mol), suggesting they may be more potent HDAC3 inhibitors. The MD simulation study of the top hit ligand-protein complex (HDAC3-ZINC000095618609 complex) revealed stable conformational changes. The results of pharmacokinetic and drug-likeness properties of the top-performing compounds reveal their potential to be considered viable HDAC3 inhibitors.</div></div><div><h3>Conclusion</h3><div>This study highlights the potential of drug repurposing as a cost-effective and faster approach to cancer treatment. here we have identified drugs have the potential to be repurposed as HDAC3 inhibitors; however, additional <em>in vitro</em> and <em>in vivo</em> studies are needed to confirm their efficacy.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"6 ","pages":"Article 100092"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470153","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}
引用次数: 0
A cautionary note on genomic complexity and bioinformatic analysis in cancer 癌症基因组复杂性和生物信息学分析的警示
Aspects of molecular medicine Pub Date : 2025-12-01 Epub Date: 2025-11-04 DOI: 10.1016/j.amolm.2025.100097
Victoria A. Patten , Hocine Bendou , Denver T. Hendricks , Christopher G. Mathew , Wenlong Carl Chen , Joanna C. Fowler , Roshan K. Sood , Philip H. Jones , M. Iqbal Parker
{"title":"A cautionary note on genomic complexity and bioinformatic analysis in cancer","authors":"Victoria A. Patten ,&nbsp;Hocine Bendou ,&nbsp;Denver T. Hendricks ,&nbsp;Christopher G. Mathew ,&nbsp;Wenlong Carl Chen ,&nbsp;Joanna C. Fowler ,&nbsp;Roshan K. Sood ,&nbsp;Philip H. Jones ,&nbsp;M. Iqbal Parker","doi":"10.1016/j.amolm.2025.100097","DOIUrl":"10.1016/j.amolm.2025.100097","url":null,"abstract":"<div><div>Variant calling in complex genomic regions remains a critical challenge in cancer genomics, yet systematic evaluations of false positive rates in such regions are rarely reported. This investigative study examined somatic mutations in esophageal squamous cell carcinoma (ESCC) using Whole Genome Sequencing (WGS) data, that identified a high frequency of putative mutations in <em>MUC3A</em>, a gene with an inherently complex sequence architecture. Quantitative laboratory validation attempts failed to confirm any of these computationally predicted mutations, prompting systematic re-analysis. By assessing multiple variant calling algorithms and implementing a Panel of Normals (PON) filtering strategy, we demonstrate that standard bioinformatics pipelines generated extensive false positive calls in <em>MUC3A</em>, with false positive rates approaching 100 % for this gene. While previous studies have acknowledged limitations in variant calling for repetitive or homologous regions, our work provides evidence of complete analytical failure in the <em>MUC3A</em> gene, and establishes a reproducible framework for identifying such artefacts. These findings address a critical research gap by quantifying the magnitude of false discovery in complex genomic contexts and demonstrating that multi-tool consensus approaches combined with PON filtering are insufficient without accompanied experimental validation. We recommend mandatory quantitative confirmation for variants identified in sequence-complex genes and advocate for transparent reporting of validation rates in cancer genomic studies to prevent propagation of spurious findings in literature. This paper provides a cautionary warning to future research to take into consideration the limitations of alignment and variant calling tools and to employ a combination of tools to obtain robust and reliable results.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"6 ","pages":"Article 100097"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465717","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}
引用次数: 0
Corrigendum to “In silico identification of potential inhibitors for the universal stress G4LZI3 protein from Schistosoma mansoni using molecular docking and molecular dynamics simulation analyses” [Aspects of Molecular Medicine 5 (2025) 100084] “基于分子对接和分子动力学模拟分析的曼氏血吸虫通用胁迫G4LZI3蛋白潜在抑制剂的计算机鉴定”[分子医学5(2025)100084]的更正
Aspects of molecular medicine Pub Date : 2025-12-01 Epub Date: 2025-08-09 DOI: 10.1016/j.amolm.2025.100096
Lihle Mahamba, Mustafa Alhaji Isa, Abidemi Paul Kappo
{"title":"Corrigendum to “In silico identification of potential inhibitors for the universal stress G4LZI3 protein from Schistosoma mansoni using molecular docking and molecular dynamics simulation analyses” [Aspects of Molecular Medicine 5 (2025) 100084]","authors":"Lihle Mahamba,&nbsp;Mustafa Alhaji Isa,&nbsp;Abidemi Paul Kappo","doi":"10.1016/j.amolm.2025.100096","DOIUrl":"10.1016/j.amolm.2025.100096","url":null,"abstract":"","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"6 ","pages":"Article 100096"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736697","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}
引用次数: 0
Hematological and biochemical responses to extreme hypoxia exposure after hypoxia preconditioning in Sprague–Dawley rats Sprague-Dawley大鼠缺氧预处理后对极度缺氧暴露的血液学和生化反应
Aspects of molecular medicine Pub Date : 2025-06-01 Epub Date: 2025-05-15 DOI: 10.1016/j.amolm.2025.100088
Megha A. Nimje , Himadri Patir , Rajesh Kumar Tirpude , Prasanna K. Reddy , Bhuvnesh Kumar
{"title":"Hematological and biochemical responses to extreme hypoxia exposure after hypoxia preconditioning in Sprague–Dawley rats","authors":"Megha A. Nimje ,&nbsp;Himadri Patir ,&nbsp;Rajesh Kumar Tirpude ,&nbsp;Prasanna K. Reddy ,&nbsp;Bhuvnesh Kumar","doi":"10.1016/j.amolm.2025.100088","DOIUrl":"10.1016/j.amolm.2025.100088","url":null,"abstract":"<div><div>Hypoxia preconditioning (HP) is postulated to induce adaptive changes in the body for endurance and hypoxic acclimatization. Its dosage (severity, intermittence, duration) determines its effectiveness. Male SD rats were subjected to HP by exposing them to intervals of hypoxia for different durations in a normobaric hypoxia chamber at 12 % FiO<sub>2</sub> for 4h consecutively for 1, 2, 3, 4 and 5 days. To assess the acclimating effect of HP, the animals were further subjected to severe hypoxic exposure to 8 % FiO<sub>2</sub> for 6h. Physiological variables (peripheral oxygen saturation-SpO<sub>2</sub>, heart rate-HR, and respiratory rate-RR), protein expression parameters (HIF-1α, EPO, VEGF, and uNOS), biochemical metabolites and hematology and blood gas variables were studied during the course of the hypoxia preconditioning schedule. All the statistical comparisons were performed using one-way ANOVA following Tukey's correction. It was found Day 3-HP was associated with a greater SpO<sub>2</sub> level (p &lt; 0.05) compared with those of other hypoxia preconditioned groups, the percentage of NRBC was lowest in day 3-HP. PCO<sub>2</sub> was lower during days 2, 3 and 4-HP. Circulatory metabolites (nitrate + nitrite-NO, L-arginine, citrulline, succinate, blood urea nitrogen, and L-lactate) changed significantly with different durations of hypoxia preconditioning. HIF-1α showed peak expression on HP-3 day, whereas EPO was highest during HP-2 day, and VEGF was significantly lower at p &lt; 0.001 as compared to extreme hypoxia without HP. Reduced oxidative stress (ROS) and inflammation (histopathology) were observed during HP-3 day. Hypoxia preconditioning at 12 % FiO<sub>2</sub> for 3 days can be postulated to be a potent non-pharmacological modality for inducing physiological and molecular responses that can influence hypoxic acclimatization during exposure to extremely hypoxic conditions.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100088"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099501","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}
引用次数: 0
Exploring new Frontiers in dry eye Disease: Treatments, mechanisms, and diagnostic innovations a comprehensive review 探索干眼病的新领域:治疗、机制和诊断创新的综合综述
Aspects of molecular medicine Pub Date : 2025-06-01 Epub Date: 2025-05-28 DOI: 10.1016/j.amolm.2025.100090
K. Narendra , Sonali K. Singh , C.K. Deepa , S. Meghana , K.R. Akanth , M. Manjushree , D. Raajasubramaniyan , S. Srinivasan , R. Murali , H.N. Sowbhagya
{"title":"Exploring new Frontiers in dry eye Disease: Treatments, mechanisms, and diagnostic innovations a comprehensive review","authors":"K. Narendra ,&nbsp;Sonali K. Singh ,&nbsp;C.K. Deepa ,&nbsp;S. Meghana ,&nbsp;K.R. Akanth ,&nbsp;M. Manjushree ,&nbsp;D. Raajasubramaniyan ,&nbsp;S. Srinivasan ,&nbsp;R. Murali ,&nbsp;H.N. Sowbhagya","doi":"10.1016/j.amolm.2025.100090","DOIUrl":"10.1016/j.amolm.2025.100090","url":null,"abstract":"<div><div>Dry Eye Disease (DED) significantly impacts quality of life through tear film instability and ocular surface inflammation. This review highlights advancements in treatments, mechanisms, and diagnostics. Emerging pharmacological therapies, including novel anti-inflammatory agents, secretagogues, corticosteroids, and autologous serum eye drops, alongside innovative devices like punctal plugs, thermal pulsation devices, and meibomian gland expression techniques. Lifestyle modifications and nutritional supplements, such as omega-3 fatty acids and antioxidants, are also explored.</div><div>Mechanistic insights cover tear film instability, inflammatory pathways, neuropathic pain, and meibomian gland dysfunction, emphasizing recent findings on the ocular surface microbiome, genetic and epigenetic factors, and chronic inflammation. Diagnostic innovations include AI and machine learning integration, advanced imaging techniques, tear film analysis, and functional tests, enhancing early detection and monitoring.</div><div>Emerging research on gene therapy, stem cell therapy, ocular surface microbiota, and gene editing technologies like CRISPR is examined for future treatment potential. Personalized medicine approaches, incorporating genomic and proteomic profiling and patient-reported outcomes, are emphasized for tailored therapies.</div><div>Environmental and lifestyle factors, including pollution, climate change, diet, and behavioral modifications, are considered for their impact on DED management. Integrating these advancements into clinical practice aims to improve patient outcomes and quality of life, highlighting the future potential of cutting-edge research and innovations.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100090"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204306","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}
引用次数: 0
Unveiling the molecular mechanisms and clinical implications of maslinic acid in diabetes mellitus: Insights from network pharmacology 揭示山茱萸酸在糖尿病中的分子机制和临床意义:来自网络药理学的见解
Aspects of molecular medicine Pub Date : 2025-06-01 Epub Date: 2024-12-10 DOI: 10.1016/j.amolm.2024.100060
Sarvesh Sabarathinam , Sanjana Satheesh
{"title":"Unveiling the molecular mechanisms and clinical implications of maslinic acid in diabetes mellitus: Insights from network pharmacology","authors":"Sarvesh Sabarathinam ,&nbsp;Sanjana Satheesh","doi":"10.1016/j.amolm.2024.100060","DOIUrl":"10.1016/j.amolm.2024.100060","url":null,"abstract":"<div><div>Maslinic acid(MA), a natural pentacyclic triterpene, has potent anti-tumor activity and exerts effects by various mechanisms, including apoptosis, cell cycle arrest, autophagy regulation, and angiogenesis alteration. We investigated the Network pharmacology and Molecular docking analysis of Maslinic Acid The network pharmacology report shows that 23 overlapping targets were identified with Maslinic Acid. Followed by the binding scores were found to be similar to the reference standard Rosiglitazone &amp; Pioglitazone. Maslinic Acid exerts its effect on insulin resistance via inhibition of peroxisome proliferator-activated receptor, α-amylase, and α-glucosidase inhibition, glycogen phosphorylase inhibition, reduction in ghrelin concentration, downregulation of SGLT1 and GLUT2 genes, NF-κB suppression, Nrf2 activation, and AMPK/SIRT 1 pathway activation. The Network analysis and docking score confirm the diabetic activity of Maslinic Acid. This study aims to study various targets of Maslinic Acid in correlation to Diabetes mellitus and analyze their mechanism in detail. Our investigation of MA as a potential treatment target for insulin resistance or diabetes mellitus using network pharmacology revealed that it has significant roles in producing glucose-lowering activity by regulating glucose homeostasis via several insulin signaling pathways discussed above.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100060"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143146628","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
Mutational analysis of antibiotic resistance genes in Helicobacter pylori from Ghanaian dyspepsia patients: Implications for treatment strategies 加纳消化不良患者幽门螺杆菌抗生素耐药基因的突变分析:对治疗策略的影响
Aspects of molecular medicine Pub Date : 2025-06-01 Epub Date: 2025-03-26 DOI: 10.1016/j.amolm.2025.100078
Eric Gyamerah Ofori , Foster Kyei , Emmanuel Ayitey Tagoe , Ansumana Sandy Bockarie , Samuel Mawuli Adadey , Osbourne Quaye , Michael Buenor Adinortey , Gordon Akanzuwine Awandare , Cynthia Ayefoumi Adinortey
{"title":"Mutational analysis of antibiotic resistance genes in Helicobacter pylori from Ghanaian dyspepsia patients: Implications for treatment strategies","authors":"Eric Gyamerah Ofori ,&nbsp;Foster Kyei ,&nbsp;Emmanuel Ayitey Tagoe ,&nbsp;Ansumana Sandy Bockarie ,&nbsp;Samuel Mawuli Adadey ,&nbsp;Osbourne Quaye ,&nbsp;Michael Buenor Adinortey ,&nbsp;Gordon Akanzuwine Awandare ,&nbsp;Cynthia Ayefoumi Adinortey","doi":"10.1016/j.amolm.2025.100078","DOIUrl":"10.1016/j.amolm.2025.100078","url":null,"abstract":"<div><h3>Background</h3><div>Antibiotic resistance jeopardizes the effectiveness of conventional treatment regimens for <em>Helicobacter pylori</em> infections, and this remains a major global health concern. <em>H. pylori</em> genes mutations negatively affect actions of most first line antibiotics. This study aimed to perform mutational analysis on <em>H. pylori</em> antibiotic resistance genes in Ghanaian patients diagnosed with dyspepsia.</div></div><div><h3>Materials and methods</h3><div>Antrum gastric biopsies were taken from 169 study participants, minced in Brain Heart Infusion broth and cultured. Sensitivity to antibiotics of <em>H. pylori</em> isolates was determined by disc diffusion. Extracted DNA were amplified and antibiotic resistance genes <em>gyrA</em>, <em>pbp1</em>, and <em>rdxA</em> sequenced. Resistance genes were analysed for base and point mutations using online databases and Ugene 45.0 software.</div></div><div><h3>Results</h3><div>Using rapid urease test, <em>H. pylori</em> infection prevalence was estimated to be 61%. Phenotypically, no sensitivity was recorded for metronidazole, amoxicillin, clarithromycin, and amoxicillin-clavulanic acid against the tested isolates. Resistance to levofloxacin was found to be 40% while 20% was recorded for each of tetracycline and ciprofloxacin. Mutations identified included G242 C/A, T254I, and S417T for <em>pbp1</em> gene in amoxicillin resistance; K2N, Q6H, Q50Stop, E75K, R90K, G98S, H99P, R131K, and A183V for <em>rdxA</em> gene; N87I/T, A97V, M191I, V199 M/A, H200Y, and G208E for <em>gyrA</em> gene in levofloxacin resistance.</div></div><div><h3>Conclusions</h3><div>There is high <em>H. pylori</em> antibiotic resistance in the region with amoxicillin, metronidazole, amoxicillin-clavulanic acid and clarithromycin showing no sensitivity to tested isolates. Tetracycline and ciprofloxacin may be more appropriate therapeutic regimen options against <em>H. pylori</em>. Observed resistance could be due to mutations in <em>rdxA</em>, <em>pbp1,</em> and <em>gyrA</em> genes.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100078"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724093","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
Discovery of natural compounds as novel FMS-like tyrosine kinase-3 (FLT3) therapeutic inhibitors for the treatment of acute myeloid leukemia: An in-silico approach 发现天然化合物作为新型fms样酪氨酸激酶-3 (FLT3)治疗性抑制剂用于治疗急性髓性白血病:一种计算机方法
Aspects of molecular medicine Pub Date : 2025-06-01 Epub Date: 2024-11-30 DOI: 10.1016/j.amolm.2024.100058
Uddalak Das , Lavanya Chandramouli , Akshay Uttarkar , Jitendra Kumar , Vidya Niranjan
{"title":"Discovery of natural compounds as novel FMS-like tyrosine kinase-3 (FLT3) therapeutic inhibitors for the treatment of acute myeloid leukemia: An in-silico approach","authors":"Uddalak Das ,&nbsp;Lavanya Chandramouli ,&nbsp;Akshay Uttarkar ,&nbsp;Jitendra Kumar ,&nbsp;Vidya Niranjan","doi":"10.1016/j.amolm.2024.100058","DOIUrl":"10.1016/j.amolm.2024.100058","url":null,"abstract":"<div><div>FLT3 mutations, observed in approximately 30–35% of Acute Myeloid Leukemia (AML) cases, drive leukemic proliferation and survival pathways, presenting a significant challenge in clinical management. To address this therapeutic need, we employed a comprehensive computational approach integrating pharmacophore screening, molecular docking, ADMET analysis, and molecular dynamics simulations to identify potent inhibitors targeting FLT3. Utilizing ligand-based pharmacophore models generated from experimentally proven FLT3 inhibitors from BindingDB, we screened over 400,000 natural compounds from the COCONUT database. Hits identified through pharmacophore screening underwent further evaluation via Lipinski and Golden triangle criteria to ensure drug-like properties. Molecular docking against the FLT3 receptor, combined with ADMET analyses, facilitated the prioritization of lead compounds. Subsequently, three promising candidates were subjected to molecular dynamics simulations to assess binding stability. Our findings reveal three top-performing compounds, demonstrating robust and stable binding affinity and favorable ADMET characteristics. These compounds hold promise as potential scaffolds or leads for developing novel FLT3 inhibitors in AML therapy.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100058"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143147279","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
Chalcone-related small molecules as potent antibacterial and antifungal agents: Design, synthesis, In vitro, and computational approaches 查尔酮相关小分子作为有效的抗菌和抗真菌剂:设计、合成、体外和计算方法
Aspects of molecular medicine Pub Date : 2025-06-01 Epub Date: 2025-02-15 DOI: 10.1016/j.amolm.2025.100066
Narmin Hamaamin Hussen , Larin Barzan Hussein , Aso Hameed Hasan , Shokhan Jamal Hamid , Chawan Othman Abdl , Bakhcha Sarkar , Kozhin Muhammed , Daroon Muhamad
{"title":"Chalcone-related small molecules as potent antibacterial and antifungal agents: Design, synthesis, In vitro, and computational approaches","authors":"Narmin Hamaamin Hussen ,&nbsp;Larin Barzan Hussein ,&nbsp;Aso Hameed Hasan ,&nbsp;Shokhan Jamal Hamid ,&nbsp;Chawan Othman Abdl ,&nbsp;Bakhcha Sarkar ,&nbsp;Kozhin Muhammed ,&nbsp;Daroon Muhamad","doi":"10.1016/j.amolm.2025.100066","DOIUrl":"10.1016/j.amolm.2025.100066","url":null,"abstract":"<div><div>Infectious diseases caused by bacteria and fungi are a global health concern due to resistance to traditional antimicrobial medications. A variety of chalcone-related small molecules have been designed, synthesized, and characterized small molecules using FTIR, NMR, and MS to find antimicrobial agents for treating these infections. These designed compounds (<strong>9, 11, 13</strong>) were evaluated for their potential inhibitory activity against five bacterial strains and one fungal strain using disc diffusion and MIC assays utilizing ampicillin and fluconazole as reference drugs. The MIC values ranged from 2.5 to 160 μg/mL, which can be attributed to improved membrane penetration and increased ligand-protein binding capability. Among them, molecule 9 exhibited a broad spectrum of antibacterial activity against gram-negative bacteria, with an MICs of 40 μg/mL against <em>P. aeruginosa</em> and 80 μg/mL against <em>E. coli</em>. Compound <strong>11</strong> showed potent activity against gram-positive bacteria and fungi, with a MICs of 40 μg/mL against <em>S. aureus</em> and 80 μg/mL against <em>C. albicans</em>. Furthermore, similar to <em>in vitro</em> study results, molecular docking demonstrated that compounds <strong>9</strong> and <strong>11</strong> had a better binding affinity against gram-positive and gram-negative bacteria and fungal species than reference drugs. Finally, physicochemical and drug-likeness results showed that all the compounds can pass Lipinski's rule of five, are absorbed through the GIT, and are suitable for oral administration.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100066"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437554","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
Molecular approaches based on investigating the therapeutic benefits of Moringa oleifera: Insights into biochemical and spermatological and metabolites studies 基于研究辣木治疗益处的分子方法:对生化、精子学和代谢物研究的见解
Aspects of molecular medicine Pub Date : 2025-06-01 Epub Date: 2025-02-16 DOI: 10.1016/j.amolm.2025.100065
Sudha Sankar , Subramaniam Umavathi , Ekambaram Gayathiri , Palanisamy Prakash
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