In silico pharmacology最新文献

{"title":"Inhibition of acyl-homoserine-lactone synthase in <i>Pseudomonas aeruginosa</i> biofilms by 7-O-methyl-aromadendrin by using molecular docking and molecular dynamics simulation.","authors":"Mohammad Jalal Nazari, Mohammad Tariq Anwary, Khanbaba Ghazanfar, Mohammad Edris Amiri, Sayed Yahya Hafid, Mohammad Jawad Jawad, Sayed Hussain Mosawi","doi":"10.1007/s40203-025-00350-4","DOIUrl":"https://doi.org/10.1007/s40203-025-00350-4","url":null,"abstract":"<p><p>This study investigates the potential of 7-O-methyl aromadendrin (7-OMA), a naturally occurring flavonoid-glycoside, as an inhibitor of acyl-homoserine-lactone (AHL) synthase in <i>Pseudomonas aeruginosa</i>, a key enzyme in quorum sensing and biofilm formation. Using molecular docking and molecular dynamics simulations, we evaluated the binding interactions and inhibitory effects of 7-OMA on AHL synthase. Molecular docking revealed a suitable binding affinity (-6.66 kcal/mol) between 7-OMA and the enzyme, with interactions at critical active site residues. Molecular dynamics simulations demonstrated that 7-OMA stabilizes the enzyme through hydrogen bonds and van der Waals interactions while enhancing its structural flexibility. The average RMSD of AHL synthase increased slightly in the presence of 7-OMA, indicating partial instability of the enzyme. Additionally, the average Rg value increased, suggesting that 7-OMA may expand the enzyme structure or reduce its compactness. MM-PBSA analysis confirmed the strength of these interactions, with favorable van der Waals and electrostatic contributions to the binding energy. These results suggest that 7-OMA disrupts the structural dynamics of AHL synthase, potentially inhibiting biofilm formation and reducing the virulence of <i>Pseudomonas aeruginosa</i>. The findings highlight the therapeutic potential of 7-OMA as a novel inhibitor of AHL synthase, offering a promising strategy to combat biofilm-associated infections. Future studies should focus on evaluating the bioavailability, in vivo efficacy, and clinical applicability of 7-OMA, as well as its broader activity against other multidrug-resistant pathogens.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"56"},"PeriodicalIF":0.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045802","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}

{"title":"Exploration of potential inhibitors against chikungunya envelope: an in-silico clue.","authors":"Aparna Chaudhuri, Bidyut Bandyopadhyay, Buddhadev Mondal, Aniket Sarkar, Sabyasachi Ghosh, Anindya Sundar Panja","doi":"10.1007/s40203-025-00351-3","DOIUrl":"https://doi.org/10.1007/s40203-025-00351-3","url":null,"abstract":"<p><p>Chikungunya virus (CHIKV) is a mosquito-borne virus which causes chikungunya disease. Two biological vectors <i>Aedes aegypti</i> and <i>Aedes albopictus</i> transmit CHIKV to the victim body. According to the report of the European Centre for Disease Prevention and Control, epidemics of chikungunya disease existed in 2024 over America, Africa, Europe and Asia. Although 50% CHIKV infected person show chronic clinical symptoms and several troubles associated with chikungunya, still there are no effective vaccines or medications on market. So availability of another CHIKV inhibiting materials and mechanisms are necessary. For this purpose recently plant-derived bioactive compounds with antiviral properties are used to inhibit chikungunya infection. In this present research work 69 CHIKV inhibiting active compounds were chosen for ADMET analysis. Drug likeness of active compounds was also analyzed based on Lipinski's rule of five. Based on the drug likeness, active compounds (Baicalein, Epicatechin, Genistein, Quercetin, Resveratrol<b>)</b> were finally screened for molecular docking with CHIKV envelope proteins using Auto Dock program. Among the five active compounds, Genistein showed highest binding energy for both E1 (ΔG = - 8.3 kcal/mol) and E2 (ΔG = - 7.1 kcal/mol). Molecular dynamics simulations signify that Genistein forms a stable complex with the CHIKV E1 and E2 proteins over a 50 ns period with a significant number of hydrogen bonds. So this present study concluded that Genistein will act as potent CHIKV E1 and E2 inhibiting active compounds. To evaluate efficiency or inhibiting capacity of finally selected Genistein against CHIKV, in vivo and in vitro validation should be conducted.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00351-3.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"55"},"PeriodicalIF":0.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060665","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}

{"title":"Anthelmintic activity of <i>Calotropis gigantea</i>: in silico investigation on novel target site nematode kinases.","authors":"Velan Gopalakrishnan, Thiruvenkadam Mahendiran","doi":"10.1007/s40203-025-00331-7","DOIUrl":"10.1007/s40203-025-00331-7","url":null,"abstract":"<p><p>Over one billion peoples are currently infected with a parasitic nematode, particularly in tropical regions. Helminthiasis is a medical condition characterized by an infection of parasitic worms in the human body. <i>Calotropis gigantea</i> Linn. Belongs to the Asclepiadaceae family, commonly known as \"Gaint milkweed\" or \"Crown flower\" and recognized as a traditional medicinal plant. In this study, anthelminthic potential of <i>Calotropis gigantea</i> phytoconstituents were determined. Nematode kinases EGFR, MEK1, and PLK1 have diverged from their vertebrate counterparts in their drug-binding pockets. The development of novel anthelmintics targets Kinases that hold potential as targets. This pipeline revealed three potential anthelmintic targets that include epidermal growth factor tyrosine kinase transmembrane receptor [EGFR], the Mitogen-activate protein kinase [MEK1], and polo-like kinase [PLK1]. The software used in the in silico study investigation is the pyRx virtual screening tool, Biovia Discovery Studio, mol-inspiration, and RCSB [Protein Data Bank (PDB)]. The various phytoconstituents of <i>Calotropis gigantea</i> were docked Stigmasterol, beta-sitosterol, Desmosterol, alpha-amyrin, asclepin, and others showed high binding energies in EGFR, MEK1, and PLK1 receptors. This investigational study research highlights the potential of phytoconstituents from <i>Calotropis gigantea</i> as anthelmintic activity.</p><p><strong>Graphic abstract: </strong></p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"54"},"PeriodicalIF":0.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797512","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}

{"title":"Alpha-bisabolol inhibits yeast to hyphal form transition and biofilm development in <i>Candida albicans</i>: in vitro and in silico studies.","authors":"Sayali Chougule, Shivani Patil, Tanjila Gavandi, Sargun Basrani, Ashwini K Jadhav, S Mohan Karuppayil","doi":"10.1007/s40203-025-00335-3","DOIUrl":"10.1007/s40203-025-00335-3","url":null,"abstract":"<p><p>In recent years, there has been growing concern about infections caused by <i>Candida albicans</i>, which pose a significant threat to human health. This intensifies the concern that can be largely attributed to the increasing number of people with compromised immune systems and the emergence of drug-resistant strains. Natural molecules are considered to be good alternatives to synthetic antifungal agents. The present study explored the effectiveness of alpha-bisabolol as an antifungal agent and its mechanism of action against <i>C. albicans</i> ATCC90028. α-bisabolol effectively inhibited various pathogenic traits of <i>C. albicans</i> like, adhesion, yeast to hyphal switching, and development of biofilm at 1 mg/ml, 0.25 mg/ml, and 0.125 mg/ml concentration, respectively. In addition, α-bisabolol demonstrated inhibition of cell cycle propagation at the G1 phase. Ergosterol production in the <i>C. albicans</i> was suppressed by α-bisabolol treatment in a dose-dependent manner. The molecular docking study revealed α-bisabolol has a good binding energy of - 7.11 kcal/mol with 14-α-demethylase enzyme, which is crucial for ergosterol synthesis. Therefore, the cell membrane integrity may be affected by treatment with α-bisabolol. qRT-PCR studies proved that α-bisabolol treatment affects gene expression in <i>C. albicans</i>. In silico binding affinity was also analyzed for <i>RAS1</i>, <i>TUP1</i> and <i>CST20</i> in the signal transduction pathway and exhibited binding affinities for at - 7.7 kcal/mol, - 8.21 kcal/mol, and for - 5.79 kcal/mol respectively. In conclusion, α-bisabolol caused reduced biofilm, ergosterol synthesis along with altered gene expressions in <i>C. albicans</i> with no hemolysis. This study proposed α-bisabolol as an alternative antifungal agent.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"53"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782365","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}

{"title":"Molecular dynamics and experimental evaluation of piperine as a potential mTOR inhibitor in colon cancer cells.","authors":"Ifat Jan, Tabasum Ali, Rafat Ali, Nida Jamil Khan, Khurshid Iqbal Andrabi, Ghulam Nabi Bader","doi":"10.1007/s40203-025-00339-z","DOIUrl":"10.1007/s40203-025-00339-z","url":null,"abstract":"<p><p>Piperine, a natural alkaloid found in black pepper (<i>Piper nigrum</i>), has the chemical formula C₁₇H₁₉NO₃ and a molecular weight of 285.34 g/mol. This research investigated its effect on the mTOR protein, which plays a crucial role in cancer development, using molecular docking, dynamic simulations, MTT, and scratch wound assays on the HCT-116 colon cancer cell line. Molecular docking revealed that piperine exhibited a binding affinity of - 8.3 kcal/mol to the mTOR protein, which is significantly comparable to rapamycin's binding affinity of - 8.8 kcal/mol, a well-known mTOR inhibitor. This comparison highlights that piperine demonstrates a substantial ability to interact with the mTOR binding site, making it a potential candidate for further evaluation. Molecular dynamics simulation studies over 100 ns confirmed that piperine remains stable and firmly bound to the mTOR active site, binding in an ATP-competitive mode. MTT assay results revealed that piperine significantly reduced cancer cell viability, with IC50 values of 84.5 ± 0.5 µM at 24 h, 46.3 ± 0.26 µM at 48 h, and 19.73 ± 0.25 µM at 72 h, while the scratch wound assay confirmed its inhibition of cancer cell migration, suggesting potential to suppress metastasis. These findings indicate that piperine is a promising mTOR inhibitor with potential applications in cancer therapy, though further research is needed.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"52"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756789","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}

{"title":"Identification of phyto-compounds from <i>Mangifera indica</i> as inhibitors of 17β-hydroxysteroid dehydrogenase: a computational approach against prostate cancer.","authors":"Adedotun Olayemi Oluwatuyi, Olusola Olalekan Elekofehinti, Hannah Oluwaseun Popoola, Moses Orimoloye Akinjiyan, Idayat Oyinkansola Kehinde, Ifeoluwa Racheal Adetoyi, Olufemi Adebisi Akinola, Folasade O Ayodeji, Olabimpe Omolola Apeji, Adeola Victor Kolawole, Akinola Oluwadamilola Dorcas, Alonge Sunday Ayodeji","doi":"10.1007/s40203-025-00332-6","DOIUrl":"10.1007/s40203-025-00332-6","url":null,"abstract":"<p><p>Prostate cancer (PrCa) is a serious health concern for the affected people and, there is an increasing demand for a viable therapy that can address the limitations of current treatments with minimal or no adverse effects. This study aims to evaluate phytocompounds extracts of <i>Mangifera indica</i> as a potential therapy development for prostate cancer. Herein, molecular docking, QSAR, molecular mechanics/generalized born surface area (MM/GBSA) estimation, ADME screening, and molecular dynamics (MD) simulation were performed using the Schrodinger suite to identify 17β-hydroxysteroid dehydrogenase antagonist from <i>Mangifera indica</i>. The results showed that fisetin (-11.669), riboflavin (-10.918), quercetin (-10.843), gallic acid 6-phenylhexyl ester (-10.817), cianidanol (-10.608), (-)-epicatechin (-10.603), ellagic acid (-10.522), Butin (-10.124) in kcal/mol were predicted to possess greater inhibitory activities against the protein target based on their high binding energies and remarkable stability compared to the standard drug, docetaxel (-7.374 kcal/mol). Fisetin (-718.37), and riboflavin (-722.37) also have better induce fit score than docetaxel (-714.02) in kcal/mol with better pharmacokinetics profile compared to the standard drug.MD simulation over 100 ns predicts that Fisetin forms stable interactions with vital residues at the catalytic site of the protein. The observations from this study predict fisetin as a putative antagonist of 17β-hydroxysteroid dehydrogenase and should be experimentally verified as a lead compound for prostate cancer therapy.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"50"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756785","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}

{"title":"Computational investigation of antiviral peptide interactions with Mpox DNA polymerase.","authors":"Harshit Tiwari, Ashal Ilyas, Pankaj Kumar Rai, Shashank Upadhyay, Subhomoi Borkotoky","doi":"10.1007/s40203-025-00342-4","DOIUrl":"10.1007/s40203-025-00342-4","url":null,"abstract":"<p><p>The Mpox DNA polymerase (DNA pol) plays a crucial role in the viral replication process, making it an ideal target for antiviral therapies. It facilitates the synthetic process of viral DNA, which is an integral stage in the life of a virus. The inhibition of the operation of Mpox DNA pol would interfere with the multiplication of the virus and help manage the disease. Peptides have emerged as a possible therapeutic alternative against viruses due to their distinct characteristics. Peptides have broad-spectrum antiviral activity, being effective against a variety of viruses. Using computational techniques, we attempted to explore the molecular details of the interaction between antiviral peptides and Mpox DNA pol. Two databases of antiviral peptides were screened in this study. This study used molecular docking, followed by molecular dynamics (MD) simulation and post-simulation binding energy predictions. From the 19 selected peptides with activity against DNA polymerases, two peptides-DRAVPe01393 and DRAVPe01399-were identified as particularly promising candidates. These peptides exhibited stable interactions with Mpox DNA pol and demonstrated good cell penetration potential as evident from the MD simulation studies. Notably, the peptides DRAVPe01399 and DRAVPe01393 have a better binding affinity of - 60.86 kcal/mol and - 47.92 kcal/mol respectively than the control ligand Cidofovir diphosphate (- 10.79 kcal/mol). These findings could lead to the development of innovative antiviral treatments to prevent monkeypox, helping global efforts to battle this emerging infectious disease.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"49"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756579","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}

{"title":"Harnessing computational methods for uncovering structural insights into <i>Leishmania donovani</i> 3-MST: implications for drug design and target specificity.","authors":"Ravi Ranjan, Rashmi Kumari, Ashish Kumar, Saravanan Vijayakumar","doi":"10.1007/s40203-025-00340-6","DOIUrl":"10.1007/s40203-025-00340-6","url":null,"abstract":"<p><p>3-Mercaptopyruvate sulfurtransferase (3-MST) is an enzyme that plays integral roles in various biological processes. In the realm of <i>Leishmania</i>, the role of 3-MST is less explored. It is a critical player in maintaining oxidative homeostasis in <i>Leishmania</i> during stress for survival. This highlights the potential of <i>Ld</i>3-MST as an appealing drug target. However, recognising structural disparities becomes essential when a protein is present in the host and parasite. This study delves into the structural distinctions between <i>Ld</i>3-MST and <i>Hs</i>3-MST, providing valuable insights with direct implications for drug design. A standout feature of <i>Ld</i>3-MST is the elongated 70 amino acid C-terminal mainly contributing to a lid-like domain above the active site cavity, setting it apart from <i>Hs</i>3-MST. The RMSD analysis shows fluctuation due to the extended tail, while Rg and SASA confirm the open and solvent-accessible nature of Ld3-MST, especially in its active site, suggesting its ability to accommodate larger molecules. PC and FEL analysis reveals unique internal molecular dynamics of Ld3-MST, particularly in its active site. Docking studies demonstrate that <i>Ld</i>3-MST's active site can effectively accommodate molecules, highlighting its potential as a drug target. This comprehensive investigation lays the foundation for developing precise <i>Ld</i>3-MST inhibitors with promising therapeutic applications.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00340-6.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"51"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756706","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}

{"title":"Unraveling the mechanisms of antitumor action of <i>Sophora flavescens</i> flavonoids via network pharmacology and molecular simulation.","authors":"Zhongyuan Guo, Gaoyue Dong, Xiaoqian Liu, Liangmian Chen, Hong Yang, Zhimin Wang","doi":"10.1007/s40203-025-00338-0","DOIUrl":"10.1007/s40203-025-00338-0","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Cancer, particularly lung, liver, and other malignancies, remains a major global health challenge due to their high incidence, complex etiology, and resistance to conventional therapies. Flavonoids derived from &lt;i&gt;Sophora flavescens&lt;/i&gt; (Kushen) have gained attention for their potential in cancer prevention and treatment. This study uses network pharmacology, based on Traditional Chinese Medicine's holistic approach, and molecular simulation techniques to explore the anticancer mechanisms of &lt;i&gt;Sophora flavescens&lt;/i&gt; flavonoids, aiming to provide a theoretical basis for developing plant-based anticancer agents. Active compounds and their targets were identified through literature screening and target identification methods. A cancer-related protein-protein interaction (PPI) network was constructed to identify key therapeutic targets, helping to understand how these flavonoids exert multitarget anticancer effects. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses elucidated mechanisms related to cancer cell proliferation inhibition, apoptosis induction, and signaling pathway regulation. Network pharmacology analysis identified TP53, ESR1, SRC, AKT1, and MAPK1 as key anticancer targets, involved in essential biological processes like phosphorylation and protein kinase activity. KEGG analysis showed that these flavonoids modulate critical pathways, particularly PI3K-Akt and RAS/RAF/MEK/ERK. Molecular docking revealed that rutin and luteolin-7-O-gentiobioside strongly bind to MAPK1, with interaction energies of 77.1466 kcal/mol and 79.2011 kcal/mol, respectively, indicating promising anticancer effects. Additionally, compounds with different substitution positions, such as those with glycosylation at the 7-OH position or isoprenyl groups at the C-8 positions, exhibited significantly higher interaction energies. Non-covalent interaction analysis further clarified how these flavonoids enhance anticancer effects through stable binding, with hydrogen bonds and hydrophobic contacts stabilizing interactions with MAPK1. Molecular dynamics simulations also confirmed the stability of these interactions, and binding free energy calculations revealed that luteolin-7-O-gentiobioside and rutin exhibited the lowest binding free energies (- 153.7841 kcal/mol and - 132.7434 kcal/mol, respectively), significantly outperforming the original ligand (- 57.7209 kcal/mol), further supporting the therapeutic potential of these compounds. To complement these findings, in silico ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) predictions were employed to evaluate the pharmacokinetic and safety profiles of rutin and luteolin-7-O-gentiobioside. The systematic analysis revealed critical issues in solubility, blood-brain barrier penetration, and hepatotoxicity, providing strategic guidance for structural optimization and formulation design. This study provides valuable insights into the multitarget anticancer me","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"48"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694962","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}

{"title":"Targeting cardiotoxicity: the potential of <i>Annona squamosa</i> L. in doxorubicin therapy.","authors":"Kshitij A Lele, Priyanka P Patil, Sneha V Kakade, Naveen R Maledavar, Shriram D Ranade, Shankar G Alegaon, Prakash R Biradar, Nayeem A Khatib","doi":"10.1007/s40203-025-00333-5","DOIUrl":"10.1007/s40203-025-00333-5","url":null,"abstract":"<p><p>Doxorubicin, a potent anthracycline used in chemotherapy, is limited by dose-dependent cardiotoxicity, leading to irreversible heart damage and heart failure. Common symptoms include fatigue, dyspnea, lower limb edema, hypotension, tachycardia, and transient arrhythmias. <i>Annona squamosa</i> L. (AS), traditionally used in medicine, was investigated for its cardioprotective action against doxorubicin-induced cardiotoxicity through computational studies. Phytocompounds were identified using literature reviews, Dr. Duke's, IMPPAT, and PubChem databases. Targets associated with Doxorubicin induced cardiotoxicity were accessed from GeneCards, and protein-protein interactions were analyzed using the STRING database. Cytoscape was used for network visualization, revealing 18 bioactives targeting 67 proteins across 14 pathways. PIK3R1 emerged as a key target with the highest interaction count among 767 targets. Molecular docking showed that the PIK3R1-Rutin complex had the lowest binding energy (- 11.873 kcal/mol), and a 100 ns molecular dynamics (MD) simulation confirmed its stability. LC-MS analysis of the crude extract indicated the presence of bioactives. In vitro antioxidant activity of AS, assessed using the DPPH assay, showed significant radical scavenging activity, correlating with the high total phenol (TPC) and total flavonoid content (TFC) detected. This integrated approach highlights AS's potential in mitigating doxorubicin-induced cardiotoxicity.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00333-5.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"47"},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665780","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}