Journal of Computer-Aided Molecular Design最新文献

{"title":"3CLpro of SARS-CoV-2 as a new target for bufadienolides: in silico and in vitro study","authors":"Muzaffar Kayumov,&nbsp;Jamoliddin Razzokov,&nbsp;Mukhriddin Makhkamov,&nbsp;Murodjon Radjabov,&nbsp;Nurkhodja Mukhamedov,&nbsp;Makhmudjon Khakimov,&nbsp;Akmal M. Asrorov,&nbsp;Okhunjon Khasanov,&nbsp;Ansor Yashinov,&nbsp;Mugrajitdin Tashmukhamedov,&nbsp;Ahmidin Wali,&nbsp;Abulimiti Yili,&nbsp;Sharafitdin Mirzaakhmedov","doi":"10.1007/s10822-025-00623-2","DOIUrl":"10.1007/s10822-025-00623-2","url":null,"abstract":"<div><p>The rapid spread of SARS-CoV-2 and its widespread public health implications have highlighted the urgent need for effective antiviral therapies. A promising strategy is to investigate natural compounds that may inhibit the key viral targets. In this work, we demonstrated the anti-SARS-CoV-2 activity of six bufadienolides, including bufalin (A), arenobufagin (B), gamabufotalin (C), telocinobufagin (D), marinobufagin (E), and bufarenogin (F) from the venom of the Central Asian green toad, <i>Bufo viridis</i>. Molecular docking assays revealed that all A-F bufadienolides bind to key residues (Thr26, His41, Met49, Met161, and Gln189) in the catalytic pocket of 3-chymotrypsin-like cysteine protease (3CL^pro), an essential enzyme for viral replication and polyprotein processing. The stability of the protein-ligand complexes was then tested using molecular dynamics (MD) simulations, while the binding free energies were estimated using the umbrella sampling (US) technique. Compounds A (-49.8 ± 1.0 kJ/mol), C (-45.9 ± 1.8 kJ/mol), E (-45.6 ± 1.1 kJ/mol), and F (-45.8 ± 1.9 kJ/mol) had significantly higher binding affinities than compounds B (-14.6 ± 1.1 kJ/mol) and D (-10.3 ± 1.9 kJ/mol). In vitro enzymatic assays also confirmed these results, demonstrating that A and C exhibited potent inhibitory activity against 3CL^pro with IC₅₀ values of 1.37 µM and 2 µM, respectively, compared to the other bufadienolides; however, they were less active than the positive control GC376 (IC₅₀ = 0.27 µM). The experimental results are consistent with the computational observations. In silico ADME profiling also revealed good pharmacokinetic properties, indicating that bufadienolides A-F are lead compounds for further antiviral drug development. Taken together, our results support the hypothesis that bufadienolides are SARS-CoV-2 3CL^pro inhibitors and elucidate their mechanism of action, thereby laying the foundation for potential therapeutic advances against COVID-19.</p></div>","PeriodicalId":621,"journal":{"name":"Journal of Computer-Aided Molecular Design","volume":"39 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144566928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantum algorithm for protein-ligand docking sites identification in the interaction space","authors":"Ioannis Liliopoulos,&nbsp;Georgios D. Varsamis,&nbsp;Theodora Karamanidou,&nbsp;Christos Papalitsas,&nbsp;Grigorios Koulouras,&nbsp;Vassilios Pantazopoulos,&nbsp;Thanos G. Stavropoulos,&nbsp;Ioannis G. Karafyllidis","doi":"10.1007/s10822-025-00620-5","DOIUrl":"10.1007/s10822-025-00620-5","url":null,"abstract":"<div><p>Over the past two decades, the development of novel drugs evolved into a high-demanding computational field. There is a constant and increasing need for advanced methods for determining protein-ligand binding in the drug design process. Even after the introduction and use of High-Performance Computers in drug design, fundamental problems and constraints have not been dealt with in a satisfactory manner. This is partially due to the fact that ligand docking in proteins is a quantum mechanical process. With the quantum computers available today, the question “Can quantum computers be used in drug design and how?” arises naturally. A novel quantum algorithm for protein-ligand docking site identification is presented here. In detail, the protein lattice model has been expanded to include protein-ligand interactions. Quantum state labelling for the interaction sites is introduced, and an extended and modified Grover quantum search algorithm is implemented to search for docking sites. This algorithm has been tested and executed on both a quantum simulator and a real quantum computer. The results show that the quantum algorithm can identify effectively docking sites. The quantum algorithm is highly scalable and well-suited for identifying docking sites within large proteins, poised to harness the potential of increased quantum bits in the future.</p></div>","PeriodicalId":621,"journal":{"name":"Journal of Computer-Aided Molecular Design","volume":"39 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144566929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling a novel ellagic acid derivative as a potent lipoxygenase (LOX) inhibitor: integration of computational modeling and experimental validation","authors":"Wali Ullah,&nbsp;Ghias Uddin,&nbsp;Abdur Rauf,&nbsp;Muhammad Umer Khan,&nbsp;Zuneera Akram,&nbsp;Chaudhry Ahmed Shabbir,&nbsp;Abdulhakeem S. Alamri,&nbsp;Walaa F. Alsanie,&nbsp;Marcello Iriti","doi":"10.1007/s10822-025-00618-z","DOIUrl":"10.1007/s10822-025-00618-z","url":null,"abstract":"<div><p><i>Cornus macrophylla</i> has been traditionally recognized for its medicinal properties, particularly in managing inflammatory conditions. However, a scientific understanding of its bioactive constituents and mechanisms remains underexplored. This study aimed to isolate and characterize bioactive compounds from the bark of <i>C. macrophylla</i> and evaluate their anti-inflammatory potential through in silico and in vitro analyses. A total of ten compounds, including an ellagic acid derivative and nine steroids and triterpenes, were isolated. Comprehensive analyses integrating molecular docking, ADMET profiling, and density functional theory (DFT) calculations were conducted to elucidate the molecular and anti-inflammatory properties. Experimental validation was performed to confirm the findings. 1,2,3-trimethoxychromeno[5,4,3-cde][1,3]dioxolo[4,5-h]chromene-5,11-dione (<b>1</b>) emerged as the most active compound among those tested, demonstrating moderate inhibition of lipoxygenase (LOX), exhibiting an IC50 value of 78.1 ± 0.03 µM. It also exhibited measurable suppression of respiratory burst activity in human neutrophils, achieving an IC50 of 298.21 ± 0.037 µM, comparable to the benchmark anti-inflammatory agent, Indomethacin (IC50: 271.14 ± 0.032 µM). Molecular docking studies revealed that compound <b>1,</b> strongly interacts with 15-LOX, demonstrating a binding affinity of -7.038 kcal/mol and forming stable interactions with key active site residues. ADMET profiling and DFT analysis indicated its favourable drug-like properties, reinforcing its potential as a therapeutic candidate. The findings highlight compound (<b>1</b>) as a potent natural inhibitor of LOX, with significant anti-inflammatory activity validated through both experimental and computational approaches. Its efficacy and drug-likeness underscore its therapeutic potential for developing novel anti-inflammatory agents. Further studies are warranted to explore its clinical applicability.</p></div>","PeriodicalId":621,"journal":{"name":"Journal of Computer-Aided Molecular Design","volume":"39 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144566930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein-ligand co-design: a case for improving binding affinity between type II NADH:quinone oxidoreductase and quinones","authors":"Vladimir Porokhin,&nbsp;Anne M. Brown,&nbsp;Soha Hassoun","doi":"10.1007/s10822-025-00613-4","DOIUrl":"10.1007/s10822-025-00613-4","url":null,"abstract":"<div><p>Biological engineering aims to enhance biological systems by designing proteins with improved catalytic properties or ligands with enhanced function. Typically, applications permit designing proteins, e.g., an enzyme in a biodegradation reaction, or ligands e.g., a drug for a target receptor, but not both. Yet, some applications can benefit from a more flexible approach where both the protein and ligand can be designed or modified together to enhance a desired property. To meet the need for this co-design capability, we introduce a novel co-design paradigm and demonstrate its application to Ndh2-quinone pairings to enhance their binding affinity. Ndh2, type-II NADH dehydrogenase, is an enzyme found in certain bacteria that facilitates extracellular electron transfer (EET) when interacting with exogenous quinone mediators. This interaction leads to the generation of a detectable electric current that can be used for biosensing applications. Our results demonstrate the benefits of the co-design paradigm in realizing Ndh2-quinone pairings with enhanced binding affinities, therefore highlighting the importance of considering protein-ligand engineering from a holistic co-design perspective.</p></div>","PeriodicalId":621,"journal":{"name":"Journal of Computer-Aided Molecular Design","volume":"39 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and evaluation of novel thiazolidinedione-oxadiazole derivatives as potent α-amylase inhibitors for antidiabetic therapy","authors":"Pinky Arora,&nbsp;Aditi Rana,&nbsp;Azmat Ali Khan,&nbsp;Amer M. Alanazi,&nbsp;Pankaj Wadhwa,&nbsp;Sonia Singla,&nbsp;Shubham Kumar,&nbsp;Rubal kalra","doi":"10.1007/s10822-025-00619-y","DOIUrl":"10.1007/s10822-025-00619-y","url":null,"abstract":"<div>\u0000 \u0000 <p>Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia. Targeting α-amylase, a key enzyme involved in carbohydrate digestion, offers an effective strategy to manage postprandial glucose levels. In this study, a series of 31 novel thiazolidinedione-oxadiazole derivatives (<b>SA1–SA31</b>) were designed using pharmacophore-based strategies to incorporate diverse electron-withdrawing (EWGs) and electron-donating groups (EDGs). Molecular docking against α-amylase (PDB ID: 4W93) revealed superior binding affinities for compounds <b>SA25</b> and <b>SA31</b> (-10.3 and − 10.6 kcal/mol, respectively) compared to the standard drug Acarbose (-6.7 kcal/mol). Structure–activity relationship (SAR) analysis highlighted the significance of <i>para</i>-positioned EWGs in enhancing binding potential. ADME analysis of the top 15 compounds demonstrated favorable pharmacokinetic profiles with high gastrointestinal absorption and no Lipinski rule violations. Eight compounds were synthesized and characterized; their α-amylase inhibitory activities were evaluated. <b>SA16</b> and <b>SA19</b> showed potent inhibition with IC₅₀ values of 9.15 µg/mL and 22.65 µg/mL, respectively. A Ramachandran plot analysis confirmed the structural validity of the target protein with 92.1% residues in favored regions. These findings underscore the potential of thiazolidinedione-oxadiazole hybrids as promising antidiabetic candidates and warrant further in vivo validation.</p>\u0000 </div>","PeriodicalId":621,"journal":{"name":"Journal of Computer-Aided Molecular Design","volume":"39 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the binding mechanism of 1,4-bis[(3-Piperidino)propanamido]anthracen-9,10-dione (1,4-BPAQ) to human telomeric G-quadruplexes: a multi-technique approach including spectroscopic, calorimetric and molecular docking insights","authors":"Priya Kumari,&nbsp;Kumud Pandav,&nbsp;Anuradha Panwar,&nbsp;Shrikant Kukreti,&nbsp;Mala Nath,&nbsp;Ritu Barthwal,&nbsp;Surat Kumar","doi":"10.1007/s10822-025-00615-2","DOIUrl":"10.1007/s10822-025-00615-2","url":null,"abstract":"<div><p>Current research suggests that anthraquinone compounds have ability to interact with G4 DNA, leading to its stabilization and potential use as telomerase inhibitors in human cells. In light of this, a series of experiments to investigate the interaction between the compound 1,4-bis[(3-Piperidino)propanamido]anthracen-9,10-dione (1,4-BPAQ) and human telomeric DNA sequences in solutions rich in K⁺ and Na⁺ solutions was conducted. Employing various biophysical techniques and titration studies, it was observed that the binding of 1,4-BPAQ to G4 sequences resulted in notable changes in absorbance, including hypochromicity followed by hyperchromicity. Furthermore, extensive fluorescence quenching (94%) was accompanied by shifts in absorbance maxima, emission wavelength, and change in ellipticity (at 265 nm and 290 nm) was found in CD spectra. The data analysis indicated possible stoichiometries of 0.5:1 and 1:1 for the drug-quadruplex DNA complexes. Presence of a red shift suggested partial stacking between bases as primary interaction mode. Interestingly, binding affinity values were moderately higher in K⁺-rich solution. In addition, a significant thermal stabilization effect of up to 25 °C in K⁺ environment, while no such stabilization was observed in Na⁺ solution upon ligand binding. Molecular docking studies revealed similar binding energies across all conformational variations, despite distinct contact patterns between the ligand and three different G4 DNA conformations (2HY9/2JPZ/143D). This research demonstrated the potential anticancer activity of 1,4-BPAQ through MTT assay, with apoptosis activity observed at lower concentrations (IC₅₀ = 5.25 µM) against HepG2 cancer cells. These structural findings may hold significance in the context of drug development for anti-cancer therapies.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":621,"journal":{"name":"Journal of Computer-Aided Molecular Design","volume":"39 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-imidazopyridine derivatives of noscapine as potent tubulin-binding anticancer agents: chemical synthesis and cellular evaluation.","authors":"Pooja Dash, Pratyush Pragyandipta, Srinivas Kantevari, Pradeep Kumar Naik","doi":"10.1007/s10822-025-00617-0","DOIUrl":"https://doi.org/10.1007/s10822-025-00617-0","url":null,"abstract":"<p><p>In this study we present a novel class of N-imidazopyridine (impy) derivatives (12-15) of noscapine by tethering the imidazo[1,2-a]pyridine core to the N-atom of the isoquinoline ring of the lead molecule noscapine. These derivatives were found to have better docking scores (- 6.213 to - 7.897 kcal/mol) than noscapine (- 4.960 kcal/mol). Further, the calculated binding energy ranged between - 25.85 to - 35.57 kcal/mol, as determined by MD simulations and MM-PBSA calculations. Tubulin binding assay also revealed higher binding affinity for compounds 12, 13, 14, and 15 with the equilibrium dissociation constant (K_D) value of 78 ± 3.8 µM, 66 ± 1.7 µM, 56 ± 1.8 µM, and 35 ± 2.4 µM, respectively. These derivatives also exhibited potent cytotoxicity against breast cancer cell lines (MCF-7 & MDA-MB-231), with IC₅₀ values ranging from 3.7 to 32.4 µM, without any toxicity to normal human embryonic kidney (HEK) cells (IC₅₀ value > 1500 µM). FACS analysis revealed early apoptotic (45%) and late apoptotic cells (35%) when treated with the N-imidazopyridine derivatives (15) and arrested the cell cycle at the G2/M phase. Moreover, the impy derivative 15 was found to reduce the volume of implanted tumor in nude mice using xenografts of MCF-7 cells without any severe toxicity. Thus, we can infer that N-imidazopyridine-noscapinoids have increased potential as anticancer agents.</p>","PeriodicalId":621,"journal":{"name":"Journal of Computer-Aided Molecular Design","volume":"39 1","pages":"36"},"PeriodicalIF":3.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenolic-based allosteric inhibition of PTP1B: unlocking new therapeutic potential for metabolic disorders.","authors":"Emadeldin M Kamel, Ahmed A Allam, Hassan A Rudayni, Fahad M Alshabrmi, Faris F Aba Alkhayl, Al Mokhtar Lamsabhi","doi":"10.1007/s10822-025-00616-1","DOIUrl":"10.1007/s10822-025-00616-1","url":null,"abstract":"<p><p>Protein tyrosine phosphatase 1B (PTP1B) plays a critical role in insulin signaling and is associated with various metabolic diseases, including type 2 diabetes. In this study, we investigated the inhibitory potential of five phenolic compounds isolated from Tamarix aphylla against PTP1B. Using molecular docking, molecular dynamics (MD) simulations, and ADMET analysis, we assessed the binding modes, stability, and pharmacokinetic properties of these compounds. The findings from in silico studies were validated by experimental in vitro enzyme activity assays, which showed that 3,3'-di-O-methylellagic acid and scutellarein exhibited the strongest inhibitory activities with IC₅₀ values of 3.77 ± 0.15 µM and 3.08 ± 0.36 µM, respectively. Both compounds were found to inhibit PTP1B via non-competitive inhibition, with K_i values of 3.90 µM and 3.40 µM. The free energy landscape (FEL) analysis confirmed stable binding conformations, while various MD parameter analyses indicated minimal structural perturbations in the enzyme, suggesting enhanced stability of the enzyme-ligand complexes. MM/PBSA calculations further supported the strong binding affinities of these compounds, highlighting their potential as PTP1B inhibitors. ADMET profiling indicated favorable pharmacokinetic properties, including good bioavailability and low toxicity risks. This study provides compelling evidence for the potential of phenolic compounds from Tamarix aphylla as therapeutic agents for PTP1B inhibition, offering new opportunities for the treatment of metabolic disorders.</p>","PeriodicalId":621,"journal":{"name":"Journal of Computer-Aided Molecular Design","volume":"39 1","pages":"35"},"PeriodicalIF":3.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An in-vitro and in-silico approaches in exploring the molecular contact of COVID-19 antiviral drug molnupiravir with human serum albumin: effect of binding on protein structure.","authors":"Mekala Prabhavathi, Bijaya Ketan Sahoo, Anna Tanuja Safala Bodapati, Bethala Samuel Raju","doi":"10.1007/s10822-025-00612-5","DOIUrl":"https://doi.org/10.1007/s10822-025-00612-5","url":null,"abstract":"<p><p>Protein structure and function are an important aspect in cellular organisms. The function of protein depends on its structural integrity. Changes in its structure may affect to its function leading to disease states. Therefore, understanding the structural integrity of protein both in its free and bound states are very important in medicinal chemistry and biophysical aspects of drug-protein interactions. The COVID-19 antiviral drug molnupiravir (MPV) was used for treatment of COVID-19 illness. The effect of MPV on secondary structure of human serum albumin (HSA) has been investigated from a biophysical perceptive using experimental and docking methods based on binding models. Binding strength of MPV with HSA was 10⁵ M^-1 order. Observed fluorescence quenching of HSA by MPV was static type with quenching constant of 10⁵ M^-1 order. Thermodynamic parameters (ΔG⁰, ∆H⁰, and ∆S⁰) suggested the spontaneity of contact with hydrogen bonding and van der Waals forces are being the primary forces. Binding-induced structural and conformational changes were visible from synchronous fluorescence and circular dichroism (CD) studies. The 3D fluorescence studies further complemented the conformational observations. Molecular docking of MPV with HSA showed its preferred location at site-1 and corroborated the experimental results. 2D diagram and ligplot assisted to analyse the interface residues in docked complex due to binding. The outcome of this study can be useful to decipher the binding behaviour of other drugs and in design of new drugs of better potential besides possible aid in pharmacodynamic studies of similar molecules.</p>","PeriodicalId":621,"journal":{"name":"Journal of Computer-Aided Molecular Design","volume":"39 1","pages":"34"},"PeriodicalIF":3.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computer-aided molecular and biological-immune modeling of illicium verum bioactive compounds employing the Egyptian Nile snail Biomphalaria alexandrina as a paradigm.","authors":"Alya Mashaal, Basma M Abou El-Nour, Fatma M Ismail, Eman A Elewa, Eman A Elnoby, Eman B Ebada, Ayaat G Mohammed, Manar F El-Sahmawy, Mariam M Mansour, Nermeen N Khames, Hend M Ghorab, Safaa A Osman, Alshimaa A Elsaid, Maryam M Abd-Alaziz, Asmaa S Zayed, Asmaa A Abo Elqasem","doi":"10.1007/s10822-025-00607-2","DOIUrl":"10.1007/s10822-025-00607-2","url":null,"abstract":"<p><p>In pursuit of sustainable biocontrol strategies, this study explores Illicium verum (star anise) as a dual-action anti-inflammatory/oxidative and molluscicidal agent using Biomphalaria alexandrina, the intermediate host of Schistosoma mansoni, as an eco-relevant in vivo model. Two experimental snail groups were employed: a control group and a treatment group exposed to a sublethal concentration of I. verum extract (LC₁₀ = 315 ppm). Through a combined pipeline of phytochemical profiling, computational simulations, and in vivo assays, we identified flavonoids and phenylpropanoids with potent bioactivity. Molecular docking and ADMET screening highlighted kaempferol, quercetin, and rutin as top ligands, which bind effectively to key snail proteins such as cytochrome c oxidase and actin. In vivo analyses confirmed immunomodulatory effects, and these findings were validated through oxidative/inflammatory biomarker assays, which revealed altered cytokine levels (IFN-γ, IL-2 and IL-6), tissue remodeling, and reduced oxidative stress. Histopathological and immunohistochemical evaluations revealed significant tissue alterations in the digestive gland and head-foot regions of treated snails. Gene and protein interaction networks supported these findings by linking compound action to immune and oxidative regulatory pathways. This integrative study demonstrated that Illicium verum contains bioactive compounds capable of modulating oxidative stress, immune responses, and tissue integrity in B. alexandrina as an animal model. Integrating phytochemical analysis with in silico and molecular simulations offers a powerful approach for understanding and optimizing bioactive compounds. While phytochemical profiling identifies key constituents such as flavonoids and phenylpropanoids, computational tools predict their binding to biological targets, pharmacokinetics, and safety. This combination not only streamlines the discovery of effective and low-toxicity compounds but also clarifies their mechanisms of action at the molecular level, enhancing both the precision and efficiency of experimental validation. These results position star anise as a promising, eco-friendly candidate for the development of novel molluscicidal and anti-inflammatory agents supporting sustainable disease control strategies.</p>","PeriodicalId":621,"journal":{"name":"Journal of Computer-Aided Molecular Design","volume":"39 1","pages":"33"},"PeriodicalIF":3.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}