Aspects of molecular medicine最新文献

{"title":"Antioxidant, anti-inflammatory and cytotoxicity properties of medicinal plants used for producing herbal products against hepatic diseases in Ghana","authors":"Dongsogo Julius ,&nbsp;Larbie Christopher ,&nbsp;Appiah-Oppong Regina ,&nbsp;Emekpe Benjamin ,&nbsp;Daniel Ataanya Abera ,&nbsp;Yusif Mubarik ,&nbsp;Iddrisu Abdul-Mumeen","doi":"10.1016/j.amolm.2025.100093","DOIUrl":"10.1016/j.amolm.2025.100093","url":null,"abstract":"<div><div>Medicinal plants have become the option for management of liver diseases because of their availability, cost effectiveness and lesser side effects compared to pharmaceutical drugs. Various parts of plants including roots, leaves, stem, bark and seed have been reportedly used to treat liver diseases including jaundice, hepatitis, hepatosteatosis, hepatocellular carcinoma, hepatobillary disorders and hepatocellular carcinoma. Phytochemicals exhibit anti-oxidant and anti-inflammatory properties due to the presence of acidic polyhydroxyl groups in the phenols. These hydroxyl groups quench free radicals from oxygen, nitrogen and sulphur reactive species thereby inhibiting oxidative stress, inflammation and fibrogenic processes. The objective of the study was to determine the antioxidant, anti-inflammatory and cytotoxicity properties of medicinal plants for the purpose of selecting more efficacious raw materials for herbal products. Ethanolic and methanolic extracts of 13 medicinal plants were test for level of total phenols, flavonoids, 2, 2-diphenyl-1-picrylhydrazyl (DPPH) reducing potential, ferric reducing (FRAP), total antioxidant binding capacity (ABTS), red cell antihemolysis assay and 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) cytotoxicity. Except for DPPH scavenging activity, there was significance of difference between the methanolic and ethanolic extracts, total phenols (p = 0.03), flavonoids (p = 0.024), FRAP (p = 0.02), ABTS (p = 0.00) and red cell hemolysis (p = 0.010). There was correlation between phytochemicals, phenols and flavonoids and antioxidant markers, DPPH, FRAP, ABTS and red cell hemolysis (p &lt; 0.05). Syzygium <em>aromaticum, Curcuma longa, Taraxacum officinalis</em> and <em>Moringa oleifera</em> exhibited the highest inhibitory anti-inflammatory and antioxidant properties. The study indicates that, phytochemical, antioxidant and inflammatory properties varied with the kind of plant, concentration of extract, extractant and polyphenol content. These properties should be evaluated in selecting materials for drug formulation.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"6 ","pages":"Article 100093"},"PeriodicalIF":0.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144605604","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":"Neurological mechanism of the dietary supplementations of lycopene on chemotherapy-induced cognitive dysfunction/chemobrain and hippocampal toxicity in the rat model","authors":"Sunday Aderemi Adelakun ,&nbsp;Jacob Adewale Siyanbade ,&nbsp;Akwu Bala Peter ,&nbsp;Mistura Abisola Salami ,&nbsp;Bisade Esther Adeyeluwa ,&nbsp;Opeyemi Zainab Kaka","doi":"10.1016/j.amolm.2025.100094","DOIUrl":"10.1016/j.amolm.2025.100094","url":null,"abstract":"<div><h3>Background</h3><div>Chemo-brain signifies the memory and cognitive challenges cancer patients encounter during and after chemotherapy. Lycopene (LP) is a naturally occurring carotenoid with potent anti-reactive oxygen species (ROS) characteristics. This study investigates the effect of Lycopene on Chemotherapy-induced cognitive dysfunction and hippocampal toxicity in rat models.</div></div><div><h3>Method</h3><div>Thirty Adult male Sprague-Dawley rats were divided into five groups of five (n = 6) rats each. Group A control received normal saline. Group B received a single dose of 10 mg/kg bwt cisplatin (CP, i.p.) on the first day. Group C received 100 mg/kg bwt of Lycopene (LP) (i.p) once daily. Group D received a single dose of 10 mg/kg CP (i.p.) on the first day, followed by 100 mg/kg bwt of LP (i.p) once daily. Group E was treated with 100 mg/kg bwt of LP (i.p) once daily, followed by a single dose of 10 mg/kg bwt CP (i.p.) on the last day. The experiment lasted for 28 days. Hippocampus histology, oxidative stress, neuro-inflammation, apoptotic markers, brain acetylcholinesterase (AChE) activity, and levels of dopamine (DA), gamma-aminobutyric acid GABA, and serotonin 5-HT were investigated.</div></div><div><h3>Results</h3><div>Lycopene attenuation of malondialdehyde and nitric oxide levels with elevated glutathione levels and intensified superoxide dismutase and catalase activities. Lycopene decreased the levels of inflammatory and apoptotic markers. In addition, LP reduced AChE activity, and elevated glial fibrillary acidic proteins increased neurotransmitter and brain-derived neurotrophic factors.</div></div><div><h3>Conclusion</h3><div>Lycopene protected chemobrain rats, decreasing inflammation and apoptosis, increasing antioxidant enzyme activities, and attenuating lipid peroxidation.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"6 ","pages":"Article 100094"},"PeriodicalIF":0.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144670925","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":"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":"2025-06-18","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}

{"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}

{"title":"Statin therapy for NAFLD: Molecular underpinnings of myopathic consequences and treatment strategies","authors":"Pratiksha Nanepag ,&nbsp;Shubhada Mangrulkar ,&nbsp;Aarti Shriwas ,&nbsp;Mayur Kale ,&nbsp;Sapana Kushwaha ,&nbsp;Nitu Wankhede ,&nbsp;Brijesh Taksande ,&nbsp;Milind Umekar","doi":"10.1016/j.amolm.2025.100091","DOIUrl":"10.1016/j.amolm.2025.100091","url":null,"abstract":"<div><div>Non-alcoholic fatty liver disease (NAFLD) encompasses a range of hepatic disorders characterized by excessive lipid accumulation in hepatocytes and is closely linked to metabolic syndrome. Statins, which are potent lipid-lowering agents, have emerged as potential therapeutic options for managing NAFLD. Recent meta-analyses have demonstrated the efficacy of statins in reducing liver enzymes, improving histological features, and attenuating disease progression in patients with NAFLD. Mechanistically, statins exert their beneficial effects by inhibiting cholesterol synthesis, modulating lipid metabolism, and exhibiting anti-inflammatory and antifibrotic properties. They target key pathogenic pathways in NAFLD, including the inhibition of sterol regulatory element-binding proteins (SREBPs), activation of peroxisome proliferator-activated receptor-alpha (PPAR-α), and enhancement of fatty acid β-oxidation. Additionally, statins mitigate hepatic inflammation by reducing pro-inflammatory cytokines and oxidative stress, while promoting fibrosis regression through the inhibition of RhoA/Rho kinase signaling and transforming growth factor-beta (TGF-β) pathways. However, statin-associated muscle symptoms (SAMS) remain a significant concern, often leading to treatment non-adherence or discontinuation. The molecular mechanisms underlying statin-induced myopathy involve the inhibition of the mevalonate pathway, coenzyme Q10 depletion, mitochondrial dysfunction, and disruption of the ubiquitin-proteasome system. Strategies to prevent and manage SAMS include alternative dosing regimens, statin switching, and the use of complementary therapies such as coenzyme Q10 and vitamin D supplementation. Novel approaches, including PCSK9 inhibitors and nutraceuticals, have also shown promise in mitigating statin-related muscle adverse effects. In conclusion, statins offer a promising therapeutic avenue for NAFLD management, particularly in patients with elevated cardiovascular risk. This review updated the statins' therapeutic potential in NAFLD, their molecular mechanisms, statin-induced myopathy, extra-hepatic effects, and preventive strategies for future research.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100091"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178313","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":"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 % FiO₂ 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 % FiO₂ for 6h. Physiological variables (peripheral oxygen saturation-SpO₂, 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 SpO₂ level (p &lt; 0.05) compared with those of other hypoxia preconditioned groups, the percentage of NRBC was lowest in day 3-HP. PCO₂ 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 % FiO₂ 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":"2025-05-15","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}

{"title":"Comprehensive review on anti-obesity effects of plant-derived compounds: Evidence from 3T3-L1 adipocytes and high-fat diet models","authors":"Sachin Gudasi,&nbsp;Mrityunjaya B. Patil","doi":"10.1016/j.amolm.2025.100089","DOIUrl":"10.1016/j.amolm.2025.100089","url":null,"abstract":"<div><div>Obesity, a multifactorial chronic disease, poses a growing global health concern, contributing to increased incidences of type 2 diabetes, cardiovascular diseases, osteoarthritis, and several cancers. Despite various pharmacological attempts targeting lipid metabolism enzymes, the associated adverse effects have led to numerous drug withdrawals, underscoring the urgent need for safer and more effective therapeutic strategies. In this context, the present study explores the <em>novel therapeutic potential</em> of plant-derived bioactives, specifically formulated using gold nanoparticles (GNPs), for the management of obesity. We systematically investigated the modulation of critical adipogenic and lipogenic regulatory proteins—C/EBP-α, PPAR-α, perilipin-1, adiponectin, FABP4, FAS, and ACC in 3T3-L1 pre-adipocytes and high-fat diet-induced obese mice. Our findings demonstrate that GNP-encapsulated phytoconstituents significantly reduce intracellular lipid accumulation by activating AMPK, a key energy sensor that downregulates pro-adipogenic and lipogenic genes (PPAR-α, C/EBP-α, AP2, SREBP-1c, ACC1, FAS, and LPL), while concurrently upregulating lipolytic and thermogenic genes (HSL, PGC-1α, and SIRT1) and enhancing adiponectin expression. The novelty of this study lies in the synergistic application of nanotechnology and traditional plant-based therapeutics to target obesity at a molecular level, offering a dual advantage of enhanced bioavailability and targeted action. These outcomes provide compelling evidence for the use of functionalized nanoparticles as a next-generation anti-obesity strategy, with potential translational value for clinical application.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100089"},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144072475","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":"In-silico identification of phytochemicals as potential therapeutic agents to inhibit the HMG-CoA reductase activity using computational approach","authors":"Sheetal Dagar ,&nbsp;Anil Panwar ,&nbsp;Dushyant Gahalyan ,&nbsp;Neeru Redhu ,&nbsp;Mukesh Kumar ,&nbsp;Sunil Kumar ,&nbsp;Varruchi Sharma ,&nbsp;Heera Ram ,&nbsp;Ravikant Verma ,&nbsp;Anil Sharma","doi":"10.1016/j.amolm.2025.100086","DOIUrl":"10.1016/j.amolm.2025.100086","url":null,"abstract":"<div><div>Phytochemicals, have long been studied for various severe metabolic illnesses and degenerative diseases like heart disease and cancer because of their significant therapeutic effects. In animal cells, cholesterol serves a critical role being a component of cell membranes and essential for the normal functioning of precursor cells to some steroid hormones. Three-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) is converted into mevalonate by the HMG-CoA Reductase (HMGCR) enzyme to produce cholesterol. However, when cholesterol levels are high, it may result in atherosclerosis. Statins, also known as synthetic drugs which decrease cholesterol, are therefore designed to work by targeting this enzyme. For patients with dyslipidemia, the side effects of excessive statin therapy have proven alarming hence using natural plant-based inhibitors is a promising alternative. Computational approach helps to identified many drugs that can target HMG-CO A Reductase. In this study, using <em>in-silico</em> molecular docking via auto-dock, 20 medicinal plants with 120 phytochemicals, reported as having antihyperlipidemic activity through deep literature study, were screened as HMG-CoA reductase enzyme inhibitors. The virtual molecular docking results reveals that five bioactive compounds; Sominone, Guggulsterone, Phytosterol, Withanolide A and Basilol, had higher binding affinities towards the HMG-CO A Reductase having binding energies of −9.33, −8.99, −8.87, −8.58, and −8.48 kcal/mol, respectively. ADMET properties of selected compounds were analysed using swiss adme tool. Results showed that out of five compounds three follow Lipinski rule of five, having ADMET properties. The HMG-CoA reductase-ligand complex's stability was validated by RMSD, RMSF, Rg, H-bond results and principal component analysis. The resulting trajectories of converged period of MD were further exploited in MM-P/G/BSA calculations to derive accurate estimates of binding free energies. This leads one to the conclusion that five phytochemicals, Sominone, Guggulsterone, Phytosterol, Withanolide A and Basilol can serve as potential inhibitors in regulating HMGCR's function may assist the development of effective anti-hyperlipedemic drugs.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100086"},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942177","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":"In silico identification of potential inhibitors for the universal stress G4LZI3 protein from Schistosoma mansoni using molecular docking and molecular dynamics simulation analyses","authors":"Lihle Mahamba,&nbsp;Mustafa Alhaji Isa,&nbsp;Abidemi Paul Kappo","doi":"10.1016/j.amolm.2025.100084","DOIUrl":"10.1016/j.amolm.2025.100084","url":null,"abstract":"<div><div><em>Human schistosomiasis</em> is a debilitating, neglected tropical disease affecting millions worldwide. Control efforts primarily rely on health education, improved sanitation, snail host management, and mass drug administration with Praziquantel (PZQ). PZQ has some limitations, such as its lower effectiveness against immature parasites and the potential for developing resistance. This requires the urgent need for new treatment approaches. The universal stress protein G4LZI3 helps the <em>Schistosoma mansoni</em> parasite survive when it is under stress from its host. Because of this, it emerges as a promising target for developing new drugs. Despite its biological relevance, G4LZI3 has not been previously investigated as a druggable target, highlighting a significant research gap in schistosomiasis drug discovery. To find potential inhibitors of G4LZI3, we conducted a virtual screening using the RASPD⁺ tool, which led us to select 7889 ligands from the CoCoNut database. These ligands were filtered based on physicochemical properties (Lipinski's Rule of Five, Veber's Rule, Egan's Filter, and the Ghose filter), pharmacokinetics, and Pan-Assay Interference Structures (PAINS) criteria, followed by molecular docking. Fifteen compounds demonstrated strong binding affinities, with binding energies ranging from −10.6 to −8.50 kcal/mol, exceeding that of PZQ (−8.4 kcal/mol). From these, six compounds were selected for further analysis, including molecular dynamics (MD) simulation, solvent-accessible surface area (SASA), and molecular mechanics generalized Born surface area (MM-GBSA) calculations. MD simulation of 200 ns revealed that CNP0475438, CNP0415153, and CNP0353858 achieved significant stability and favourable interactions with G4LZI3. These findings show these compounds as promising candidates for <em>S. mansoni</em> inhibition, pending experimental validation. The results identify novel scaffolds with vigorous predicted activity and provide a rational starting point for experimental optimization and development of new antiparasitic therapies that address praziquantel resistance and efficacy limitations in endemic regions.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100084"},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143900077","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":"Identification and exploration of novel FGFR-1 inhibitors in the Lotus database for Cholangiocarcinoma (CCA) treatment","authors":"Samuel Aduramurewa Osunnaya ,&nbsp;Wilberforce K. Ndarawit ,&nbsp;Ifeoluwa Aderibigbe ,&nbsp;Ibilola A. Omolopo ,&nbsp;Precious O. Aribisala ,&nbsp;Ayodele Oluwasegun Elekan ,&nbsp;Adeola Sakirat Adeyemo ,&nbsp;Sheriffdeen Abiola Amoo ,&nbsp;Olatunde Simbiat Olamiposi ,&nbsp;Njogu M. Kimani ,&nbsp;Taiwo Hamidat Olaide ,&nbsp;Adedoyin John-Joy Owolade ,&nbsp;Damilola Samuel Bodun","doi":"10.1016/j.amolm.2025.100085","DOIUrl":"10.1016/j.amolm.2025.100085","url":null,"abstract":"<div><div>Cholangiocarcinoma (CCA) is a rare but aggressive cancer affecting the bile duct, with limited treatment options and a poor prognosis. This study employed a machine learning algorithm and molecular docking using Maestro to screen 215,925 compounds from the Lotus database, aiming to identify potential fibroblast growth factor receptor-1 (FGFR1) inhibitors as therapeutic agents. Five promising compounds were identified, with binding energies ranging from −10.018 to −8.439 kcal/mol, all outperforming the standard drug Dovitinib (−8.419 kcal/mol). Molecular mechanics calculations and MM/GBSA analysis confirmed the structural stability and favorable binding energies of the protein-ligand complexes. Additionally, 100-ns molecular dynamic simulations demonstrated that the top three compounds remained stable within FGFR1's active site, supported by root mean square deviation, root mean square fluctuation, and hydrogen bond interactions. Overall, these five compounds show promise as potential therapeutic agents for CCA and warrant further investigation for drug development.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100085"},"PeriodicalIF":0.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917803","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}