In silico pharmacology最新文献

{"title":"Deciphering the anthelmintic mechanisms of <i>Operculina turpethum</i> through integrated computational and in vitro approaches.","authors":"Neeraj Choudhary, Ashish Suttee, Gopal L Khatik, Paranjeet Kaur, Somdutt Mujwar, Manjinder Singh","doi":"10.1007/s40203-025-00432-3","DOIUrl":"https://doi.org/10.1007/s40203-025-00432-3","url":null,"abstract":"<p><p>Ethanobotanically, <i>Operculina turpethum</i> (O.T.) exhibits various therapeutic activities, including anti-inflammatory, hepatoprotective, anticancer, antiulcer, antidiabetic, and anthelmintic activity. However, the anthelmintic property lacks systematic investigation and exploration of mechanisms and responsible phytoconstituents. To elucidate the mechanistic basis of the anthelmintic activity of <i>Operculina turpethum</i> through in silico approaches, including ADMET profiling, molecular dynamics simulations, and KEGG pathway analysis. Additionally, to comprehensively evaluate the anthelmintic efficacy of its enriched extracts against Eisenia foetida through in vitro assays. Microwave-assisted extraction of <i>Operculina turpethum</i> with various solvents (petroleum ether, ethyl acetate, methanol, hydroalcoholic, and aqueous) was carried out to obtain numerous extracts. Evaluation of anthelmintic activity against <i>Eisenia foetida</i> earthworm using Piperazine citrate (PC) as a benchmark. Characterization of the most active extract (petroleum ether) using LC-MS. Furthermore, In silico analysis, ADMET, molecular docking, KEGG, and GO analysis of phytoconstituent with the target protein was carried out. Petroleum ether extract (PE) showed the most promising anthelmintic activity compared to other extracts and in comparison to the standard drug PC. LC-MS identified viniferifuran (VIN) and arbutin (ARB) in the PE extract. VIN exhibited the highest binding affinity (- 6.1 kcal/mol) compared to the standard PC (- 2.4 kcal/mol) and GABA ligand (- 2.9 kcal/mol) in docking studies. In silico ADMET analysis predicted VIN to be non-carcinogenic and non-mutagenic. KEGG analysis revealed Viniferifuran's involvement in cAMP, cholinergic, and calcium signaling pathways, indicating its multi-target potential in mediating anthelmintic effects. PE extract displayed significant anthelmintic activity, potentially due to VIN, which acts through a GABA-mimetic mechanism. <i>Operculina turpethum</i> (O.T.) holds promise as a potential source for anthelmintic drug development.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 3","pages":"142"},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234386","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":"In silico design and assessment of a multiepitope and multiantigen potential vaccine candidate against <i>Leishmania donovani</i>.","authors":"Satabdi Saha, Sahina Laskar, Seshan Gunalan, Gugan Kothandan, Diwakar Kumar","doi":"10.1007/s40203-025-00433-2","DOIUrl":"https://doi.org/10.1007/s40203-025-00433-2","url":null,"abstract":"<p><p>Visceral Leishmaniasis (VL), primarily caused by <i>Leishmania donovani</i>, presents a formidable public health challenge, with existing therapeutic options-such as pentamidine, amphotericin B, miltefosine, and paromomycin-being limited by adverse effects, high costs, restricted availability, and the emergence of drug-resistant strains. Despite the use of combination therapies, which have achieved an approximately 85% cure rate, the lack of a safe, effective, and durable vaccine remains a critical barrier to VL eradication. This study employed a comprehensive immuno-bioinformatics approach to design and analyse a multi-epitope vaccine candidate targeting essential immunogenic proteins in <i>Leishmania spp</i>: stress-induced proteins, Prohibitin (PHB), and GP63. These proteins play crucial roles in parasite survival, virulence, and host immune modulation. Our computational analysis identified epitopes from these proteins that were predicted to elicit strong humoral and cellular immune responses while being non-allergenic. The designed vaccine construct demonstrates substantial immunogenic potential, highlighting its promise as a candidate for further preclinical and clinical evaluation in pursuing an effective VL vaccine.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00433-2.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 3","pages":"140"},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234486","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":"Metabolomic profiling, in-vitro and in-silico analysis of Ayurvedic formulation Madhumehantak Churna, identifies Ptelatoside A as a potent anti-diabetic biomolecule.","authors":"Parboni Biswas, Debarupa Hajra, Santanu Paul","doi":"10.1007/s40203-025-00430-5","DOIUrl":"https://doi.org/10.1007/s40203-025-00430-5","url":null,"abstract":"<p><p>Diabetes is a 21st-century epidemic affecting 10.1 crores Indians as of 2023. Ayurveda, a traditional indigenous medical practice, can be leveraged to manage diabetes, as the allopathic antihyperglycemic drugs are reported to cause severe repercussions. This study employs a combinatorial integrated approach to explore the scientific anti-diabetic prophylaxis of Madhumehantak Churna, an Ayurvedic formulation. Hydroalcoholic extract of Madhumehantak Churna (MCH) exhibited robust in-vitro enzyme inhibition and antioxidant assays. Out of 36 major phytocompounds identified by LC-MS profiling in MCH, ProTox 3.0 identified 29 phytocompounds with no significant toxicity, screened based on their toxicity (LD₅₀). These were subjected to integrated Network pharmacology and bioinformatics, involving in-silico molecular docking, ADMET, homology modelling and simulation studies. In-silico molecular docking studies of 29 compounds with 28 proteins, including GLUT12, Myeloperoxidase, Phosphodiesterase 4D, Cathepsin B, Cathepsin S identified from literature studies and network pharmacology, devised by STRING and CYTOSCAPE, highlighted that Ptelatoside A showed the strongest binding affinities. In-silico pharmacokinetics and ADMET analysis predicted Ptelatoside A, a glucoside, to possess the requisite drug likeness parameters. GROMACS-assisted Molecular dynamics simulation (MDS), PCA and KEGG pathway identified insulin resistance and insulin signalling pathways as the probable underlying molecular actions of Ptelatoside A against diabetes mellitus. The combinatorial study involving in-vitro anti-diabetic assessments, network pharmacology, molecular docking, in-silico pharmacokinetics, PCA analysis and simulation studies, underscores that the glycoside Ptelatoside A from the Ayurvedic formulation, Madhumehantak Churna, can be a future solution for anti-hyperglycemic drug development.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00430-5.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 3","pages":"141"},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234519","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":"Computer-aided design process of possible antisickling agents using molecular docking, pharmacokinetic assessment, homology modeling, and molecular dynamic studies targeting Hba protein.","authors":"Stephen Ejeh, Habiba Asipita Otaru, Muhammad Tukur Ibrahim, Abdullahi Bello Umar, John Enyi Ejeh, Abduljelil Ajala, Samuel Ndaghiya Adawara, Ramith Ramu, Fabian Audu Ugbe, Joshua John, Idongesit Bassey Anweting","doi":"10.1007/s40203-025-00424-3","DOIUrl":"https://doi.org/10.1007/s40203-025-00424-3","url":null,"abstract":"<p><p>Sickle cell disease (SCD), a multiorgan disease that is one of the most common genetic ailments, affects about 15 million people globally. The findings for drugs that bind to hemoglobin and adjust the oxygenation condition have been a key component of SCD treatment. The goal of this study was to use computational methods to find lead compounds, design novel bioactive molecules that are strong SCD inhibitors, and gain further knowledge about their reaction process. With data demonstrating predictive properties of <i>R</i> ² = 0.990, [Formula: see text] = 0.980, and [Formula: see text] = 0.987, the developed QSAR model is statistically reliable and highly predictive. It also satisfies the established standards for sound models, which are recommended by numerous institutions. According to the study, the designed molecules (DM) exhibit predicted biological activity (pIC₅₀) of 6.843, 6.671, and 6.912 in comparison to pIC₅₀ of 5.403 for the TM and 4.956 for the SD. Additionally, molecules DM1, DM2, and DM3 exhibit better drug ratings of 0.67, 0.56, and 0.91, respectively, compared to drug scores of 0.44 for TM and 0.49 for SD, suggesting better pharmacokinetic properties than TM and SD. The protein-DM3 complex showed higher binding free energies than the protein-L-glutamate complex, indicating that it is more stable, according to MD simulation, which was used to determine the stability of the proposed molecule.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 3","pages":"143"},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234298","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":"Anti alpha-amylase and alpha-glucosidase activities of the ethanolic leaf extracts of <i>Nephrolepis cordifolia</i> (L.) C.Presl.","authors":"Ningthoujam Seema Devi, Niraj Singh, Setu Chakrabarty, Lonika Nongsiej, Daphikerlin Kharmalki, Taranga Jyoti Baruah","doi":"10.1007/s40203-025-00435-0","DOIUrl":"https://doi.org/10.1007/s40203-025-00435-0","url":null,"abstract":"<p><p>Inhibition of alpha-amylase and alpha-glucosidase enzymes is considered a therapeutic measure for the management of diabetes. <i>Nephrolepis cordifolia</i> (L.) C.Presl is a plant that is utilised by the indigenous communities of North East India for its medicinal properties. Previous studies have predicted its potential as an anti-diabetic agent. In our study, we carried out an in-silico study of the binding ability of the reported phytochemicals of <i>N. cordifolia</i> leaf extract to the enzymes alpha-amylase and alpha-glucosidase. That was followed by the molecular simulation dynamics studies. In-vitro assays were carried out to check the inhibitory activity of the leaf extract of <i>N. cordifolia</i> upon the activities of alpha-amylase and alpha-glucosidase. Docking studies revealed fernene as the phytochemical present in the leaf extract that showed the best binding values against the enzymes. Molecular dynamics studies revealed a steady binding of fernene when bound to the enzymes. Fernene showed favourable ADMET properties. The ethanolic extract of <i>N. cordifolia</i> was able to lower the activity of both enzymes. Our results show that the leaf extract of <i>N. cordifolia</i> holds considerable ground for further exploration of its anti-diabetic activity.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00435-0.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 3","pages":"144"},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234716","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":"Using immunoinformatics and bioinformatics approach to design novel and effective rational in-silico vaccine against human <i>Astrovirus</i> targeting the capsid polyprotein VP90: a silent threat to global gastrointestinal tract.","authors":"Itazaz Ul Haq, Najeeb Ullah, Muhammad Rahiyab, Ruqia Sartaj, Ishaq Khan, Syed Shujait Ali, Fazal Akbar, Arshad Iqbal","doi":"10.1007/s40203-025-00428-z","DOIUrl":"https://doi.org/10.1007/s40203-025-00428-z","url":null,"abstract":"<p><p>The human <i>Astrovirus</i>, classified within the family <i>Astroviridae</i> and genus Mammastrovirus, is a significant pathogen predominantly affecting immunocompromised individuals and young children, and it is the causative agent of viral gastroenteritis. Currently, there are no effective antiviral treatments or vaccines in stock for <i>HAstV</i> illness, demonstrating the urgent need for vaccine development against this disease. This study used the Capsid Polyprotein VP90 to predict B-cell, CTL and HTL epitopes using precise Immunoinformatics approach. Non-allergenic and immunogenic epitopes were selected for the formulation of a subunit vaccine. Appropriate linkers, namely KK, GPGPG, and AAY, were employed to connect these epitopes. Immune simulation revealed elevated IgM and IgG titers (> 600,000/ml), accompanied by increased cytokine production (IFN-γ ≈ 430,000/ml; IL-2 ≈ 180,000/ml), demonstrating a strong and balanced humoral and cellular immune response. The antigenicity and immunogenicity examination resulted in antigenicity values of 0.5997 and 0.939735 respectively. The structural model of the vaccine was generated and validated using ProSA, Rampage, and ERRAT servers, yielding a Z-score of - 7.53, an ERRAT value of 97.004, and a Ramachandran plot that demonstrated 93.0% of residues were located within the favored region. Subsequent docking analyses indicated that TLR7 exhibited a strong binding affinity towards the vaccine model, characterized by 219 non-bonding contacts, 4 salt bridges, and 14 hydrogen bonds. The vaccine sequence, reverse-translated for optimal expression, was cloned into the pET28a ( +) vector. To optimize the vaccine developed in this research, further experimental validation is warranted.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 3","pages":"139"},"PeriodicalIF":0.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187990","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":"In silico ligand self-assembly drives binding recognition of natural products into <i>Anopheles gambiae</i> cytosolic sulfotransferases (AgSULT-001425) protein.","authors":"Angelina I Makaye, Lucas Paul, Said A H Vuai, Daniel M Shadrack","doi":"10.1007/s40203-025-00403-8","DOIUrl":"https://doi.org/10.1007/s40203-025-00403-8","url":null,"abstract":"<p><p>Malaria remains one of the most devastating diseases affecting humanity, generating a significant interest in developing effective and reliable interventions. Synthetic insecticides widely used for vector control face limitations due to increased insect resistance and toxicity to humans and non-target species. Indole alkaloids, recognized for their insecticidal properties, have emerged as promising alternatives, however, their molecular mechanisms and efficacy for malaria vector control have not been fully explored or documented. AgSULT-001425, a sulfotransferase enzyme crucial for mosquito development and reproductive success, represents a key target for disrupting mosquito survival. To investigate this, molecular docking, dynamics, and MMPBSA analyses were employed to explore the binding mechanisms, stability, and self-assembly of indole alkaloids with AgSULT-001425. The binding affinity was ranked as EP4 > ST6 > AS4 > SP4. Hydrated docking indicated that EP4-7R0U binding affinity improved significantly to - 10.41 kcal/mol, surpassing the binding affinity of the co-crystallized ligand by - 1.0 kcal/mol. ADME/T analysis confirmed drug-like properties and high bioavailability with adherence to Lipinski's rule of five. Stability analyses demonstrated minimal structural deviations, compact protein structures ensuring stable interactions. MMPBSA identified EP4 (- 94.83 kJ/mol) and ST6 (- 91.67 kJ/mol) as exhibiting the strongest binding energies. During self-assembly, SP4 achieved the shortest distance to the protein, whereas the free energy surface emphasized stable interactions for both EP4 and SP4. Based on these findings, the identified natural inhibitors demonstrate potential as lead compounds for developing more potent insecticides. However, experimental validation is needed to confirm their efficacy and optimize their properties for practical use.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00403-8.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 3","pages":"138"},"PeriodicalIF":0.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115690","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":"Naringenin and its structural analogues inhibit CDK2: a combined MD-MMGBSA and protein-ligand interaction study for colon cancer.","authors":"Francis Dhiya, K S Sindhu, J Kavitha, Varughese Jibin, Vincent Maria, T G Abi","doi":"10.1007/s40203-025-00420-7","DOIUrl":"https://doi.org/10.1007/s40203-025-00420-7","url":null,"abstract":"<p><p>Cyclin-dependent kinase 2 (CDK2) is an important regulatory factor of the G1-S phase transition of the cell cycle, and a promising target for developing therapies to treat colon cancer. In this study, Naringenin and versions of its structure (Poriol, 7-Hydroxyflavanone, and Farrerol) were evaluated for their inhibitory potential using a multi-level in silico approach involving molecular docking, density functional theory (DFT), molecular dynamics (MD) simulation, and MMGBSA binding free energy. Naringenin bound with the most favourable affinity (ΔG_bind = - 43.55 kcal/mol) to CDK2, which stabilized binding through important active site residue contacts (LEU83, ILE10, and VAL18). DFT derived reactivity descriptors and electrostatic potential maps identified the carbonyl group as a key site of protein-ligand recognition. After 200 ns of MD simulation, Naringenin had a stable structure (i.e., RMSD values), and MMGBSA and residue decomposition analyses of each molecule supported favourable binding space energetically. Overall, our study indicated that Naringenin may be a lead compound in drug development targeting CDK2. However, the anticancer potential and pharmacokinetic properties need to be validated with in vitro and in vivo studies. This study demonstrates a rational basis to move Naringenin-based scaffolds forward in preclinical cancer research by employing computational and translational pharmacology.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00420-7.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 3","pages":"137"},"PeriodicalIF":0.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115642","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 Acute Myeloid Leukemia with 1,2,4-triazolo[4,3-b]pyridazine derivatives: a molecular docking, dynamics, and ADMET approach.","authors":"Vincent A Obakachi, Krishna K Govender, Penny P Govender","doi":"10.1007/s40203-025-00418-1","DOIUrl":"10.1007/s40203-025-00418-1","url":null,"abstract":"<p><p>Acute Myeloid Leukemia (AML) remains a critical therapeutic challenge, warranting the development of novel inhibitors targeting essential survival proteins such as Myeloid Cell Leukemia-1 (Mcl-1). In this purely computational study, a series of 1,2,4-triazolo[4,3-b]pyridazine derivatives were assessed for their potential as Mcl-1 inhibitors through molecular docking, molecular dynamics (MD) simulations, quantum chemical calculations, and ADMET profiling. Docking identified compounds <b>8f</b>, <b>8j</b>, <b>8k</b>, and <b>8l</b> as promising candidates, with <b>8l</b> exhibiting the most favorable binding free energy (ΔG_bind = - 58.96 kcal/mol). Docking-derived inhibition constants (<i>Ki</i>) revealed that <b>8f</b>, <b>8j</b>, <b>8k</b>, and <b>8l</b> had <i>Ki</i> values of 0.31 µM, 0.32 µM, 0.35 µM, and 0.34 µM, respectively, while Sunitinib showed a slightly weaker <i>Ki</i> of 0.36 µM. MD simulations demonstrated increased structural stability of the protein-ligand complexes, with RMSD values ranging from 1.68 Å (8f) to 1.90 Å (<b>8j</b>), compared to the unbound APO structure (2.12 Å). Compound <b>8l</b> maintained a low RMSD (1.71 Å) and favorable flexibility profile (RMSF = 0.89 Å), comparable to Sunitinib (RMSF = 0.76 Å). DFT analysis highlighted 8l's high electronic reactivity, with a HOMO-LUMO gap of 3.18 eV in DMF. Although prior experimental studies confirmed <b>8l</b> potent anti-AML activity (IC₅₀ = 1.5 µM), ADMET predictions revealed pharmacokinetic limitations, including low solubility and permeability. These findings position compound <b>8l</b> as a compelling lead candidate for AML therapy and provide a strong foundation for future optimization aimed at improving its pharmacokinetic profile and dynamic stability. To substantiate these computational findings, we will initiate experimental validation studies involving Mcl-1 binding assays and cytotoxicity evaluation in AML cell lines.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00418-1.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 3","pages":"135"},"PeriodicalIF":0.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115708","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":"In silico evaluation of berberine and silymarin against metabolic targets: a rationale for OMICS technology-based co-formulation.","authors":"Augustine Amalraj, V Anantha Narayanan, T S Ardra, Sreeraj Gopi","doi":"10.1007/s40203-025-00426-1","DOIUrl":"https://doi.org/10.1007/s40203-025-00426-1","url":null,"abstract":"<p><p>Berberine and silymarin are phytochemicals with established pleiotropic effects across glucose, lipid, and inflammatory pathways, making them promising candidates for managing metabolic disorders such as type 2 diabetes mellitus (T2DM) and dyslipidaemia. However, their clinical translation is hindered by poor solubility, low permeability, and metabolic instability. This study aimed to evaluate the pharmacokinetic and pharmacodynamic profiles of berberine and silymarin using in silico tools and propose a rational design for an OMICS technology-based co-formulation to enhance their therapeutic potential. Comprehensive in silico analyses were performed, including molecular docking against DPP4, PTP1B, PCSK9, and P38MAPK, ADMET profiling, CYP450 interaction prediction, toxicity screening, and canonical SMILES-based structural assessment. Berberine showed good GI and BBB permeability with strong target binding (- 7.1 to - 8.0 kcal/mol) but presented liabilities including P-gp efflux and CYP inhibition. Silymarin exhibited stronger docking scores (up to - 9.0 kcal/mol) and favourable safety but limited permeability. Their complementary profiles support co-formulation. Findings support the development of an OMICS technology-based lipid-protein encapsulated formulation to overcome pharmacokinetic barriers and enhance synergistic efficacy. This approach holds promise for optimized multi-target management of T2DM and related metabolic disorders.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 3","pages":"136"},"PeriodicalIF":0.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115723","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}