In silico pharmacology最新文献

{"title":"In silico design and assessment of a multi-epitope peptide vaccine against multidrug-resistant <i>Acinetobacter baumannii</i>.","authors":"Shiv Nandan Sah, Sumit Gupta, Neha Bhardwaj, Lalit Kumar Gautam, Neena Capalash, Prince Sharma","doi":"10.1007/s40203-024-00292-3","DOIUrl":"10.1007/s40203-024-00292-3","url":null,"abstract":"<p><p><i>Acinetobacter baumannii</i>, an opportunistic and notorious nosocomial pathogen, is responsible for many infections affecting soft tissues, skin, lungs, bloodstream, and urinary tract, accounting for more than 722,000 cases annually. Despite the numerous advancements in therapeutic options, no approved vaccine is currently available for this particular bacterium. Consequently, this study focused on creating a rational vaccine design using bioinformatics tools. Three outer membrane proteins with immunogenic potential and properties of good vaccine candidates were used to select epitopes based on good antigenic properties, non-allergenicity, high binding scores, and a low IC50 value. A multi-epitope peptide (MEP) construct was created by sequentially linking the epitopes using suitable linkers. ClusPro 2.0 and C-ImmSim web servers were used for docking analysis with TLR2/TLR4 and immune response respectively. The Ramachandran plot showed an accurate model of the MEP with 100% residue in the most favored and allowed regions. The construct was highly antigenic, stable, non-allergenic, non-toxic, and soluble, and showed maximum population coverage. Additionally, molecular docking demonstrated strong binding between the designed MEP vaccine and TLR2/TLR4. In silico immunological simulations showed significant increases in T-cell and B-cell populations. Finally, codon optimization and in silico cloning were conducted using the pET-28a (+) plasmid vector to evaluate the efficiency of the expression of vaccine peptide in the host organism (<i>Escherichia coli</i>). This designed MEP vaccine would support and accelerate the laboratory work to develop a potent vaccine targeting MDR <i>Acinetobacter baumannii</i>.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00292-3.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901437","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":"Repurposing fluvoxamine as an inhibitor for NUDT5 in breast cancer cell: an in silico and in vitro study.","authors":"Sumathi Ramasamy, Kanimozhi Jeyaram, Aathimoolam Narayanan, Sankarganesh Arunachalam, Selvarajan Ethiraj, Muthumanickam Sankar, Boomi Pandian","doi":"10.1007/s40203-024-00293-2","DOIUrl":"10.1007/s40203-024-00293-2","url":null,"abstract":"<p><p>Drug repurposing is necessary to accelerate drug discovery and meet the drug needs. This study investigated the possibility of using fluvoxamine to inhibit the cellular metabolizing enzyme NUDT5 in breast cancer. Computational and experimental techniques were used to evaluate the structural flexibility, binding stability, and chemical reactivity of the drugs. These findings indicated that fluvoxamine effectively suppressed the activity of NUDT5, as evidenced by a binding score of - 8.514 kcal/mol. Furthermore, the binding positions of fluvoxamine and NUDT5 were optimized. Fluvoxamine attachment to the active sites of Trp28, Trp46, Glu47, Arg51, Arg84, and Leu98 in NUDT5 has been shown to alter the metabolism of ADPr. These alterations play a role in ATP production in the breast cancer cells. In addition, an MTT assay conducted on the MCF-7 cell line using fluvoxamine revealed an IC50 value of 53.86 ± 0.05 µM. Fluvoxamine-induced apoptosis was confirmed as evidenced by AO/EtBr and DAPI staining.</p><p><strong>Graphical abstract: </strong>Effect of fluvoxamine on breast cancer cells.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899920","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":"Network pharmacology-integrated molecular modeling analysis of <i>Aquilaria malaccensis</i> L. (agarwood) essential oil phytocompounds.","authors":"Prajisha Jayaprakash, Twahira Begum, Mohan Lal","doi":"10.1007/s40203-024-00289-y","DOIUrl":"10.1007/s40203-024-00289-y","url":null,"abstract":"<p><p>A network pharmacology approach was used to construct comprehensive pharmacological networks, elucidating the interactions between agarwood compounds and key biological targets associated with cancer pathways. We have employed a combination of network pharmacology, molecular docking and molecular dynamics to unravel agarwood plants' active components and potential mechanisms. Reported 23 molecules were collected from the agarwood plants and considered to identify molecular targets. Further, we identified ten potent targets related to cancer through network pharmacology analysis. The key targets include EGFR, JUN, TP53, SRC, MAPK3, ACTB, GAPDH, AKT1, MYC and CTNNB1. The biological processes include the negative regulation of fibroblast proliferation, metabolic, oxidative, and more. Subsequently, molecular docking results have indicated that 7-isopropenyl-1, 4a-dimethyl-4, 4a, 5,6,7,8-hexahydro-3 H-naphthalen-2-one showed an excellent binding affinity for all ten targets. This is the first study; we employed a novel integrated approach that combines network pharmacology, molecular docking and molecular dynamics simulation (MDS). The GO and KEGG, pathway enrichment analyses, shed light on biological processes relevant to cancer treatment. Moreover, molecular docking studies results indicated that the molecule 7-isopropenyl-1,4a-dimethyl-4,4a,5,6,7,8-hexahydro-3H-naphthalen-2-one exhibited strong binding affinity among all ten cancer targets, with a docking score ranging from - 9.9 to - 6.7 kcal/mol and found to have hydrogen bond interaction with Lys168, Ser322, Thr336 and Ala946 residues. MDS sheds light on the stability of their binding, the longevity of their interactions, and their overall effect on the enzyme's active site throughout the simulation. The current work signifies the initial report using bioinformatics approaches to assess the anticancer properties of compounds derived from the agarwood plant.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901439","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 vitro and in silico approaches manifest the anti-leishmanial activity of wild edible mushroom <i>Amanita princeps</i>.","authors":"Ishita Bhattacharya, Nibedita Pyne, Santanu Paul","doi":"10.1007/s40203-024-00287-0","DOIUrl":"10.1007/s40203-024-00287-0","url":null,"abstract":"<p><p>Visceral Leishmaniasis, caused by <i>Leishmania donovani,</i> is the second most deadly parasitic disease, causing over 65,000 deaths annually. Synthetic drugs available in the market, to combat this disease, have numerous side effects. In this backdrop, we aim to find safer antileishmanial alternatives with minimal side effects from mushrooms, which harbour various secondary metabolites with promising efficacy. Robust screening of sixteen extracts from eight different wild mushrooms reveals that the hydroalcoholic extract of <i>Amanita princeps</i> has outstanding antileishmanial activity against <i>Leishmania donovani</i>. Metabolomic profiling of this lead extract identifies 50 bioactive mycocompounds and among them, 10 were selected for <i>in-silico</i> study against five major targets-arginase, spermidine synthase, ornithine decarboxylase, trypanothione reductase and SOD, crucial for thiol-redox balance in parasites in the polyamine synthesis pathway. Molecular docking analysis against our prioritised targets identified two mycompounds Ergosterol and Taraxacolide 1-O-b-D-glucopyranoside from <i>Amanita princeps</i> having the highest binding affinity of -15.8 and -11.8 kcal/mol respectively against the ornithine decarboxylase of polyamine synthesis pathway. However, MD simulations and free energy calculation using MM-GBSA analysis revealed the better stability of ergosterol with PASP receptors suggesting its promising role as an anti-leishmanial compound. Further results of in vitro arginase, SOD, and NO enzyme assays also corroborated with <i>in-silico</i> findings, reinforcing the anti-leishmanial efficacy of the <i>Amanita princeps</i> extract. Thus, both in silico and in vitro analyses suggest the efficacy of both Ergosterol and Taraxacolide 1-O-b-D-glucopyranoside compounds resourced from <i>Amanita princeps</i> as potent antileishmanial agents.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901438","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":"Immunoinformatics-driven design and computational analysis of a multiepitope vaccine targeting uropathogenic <i>Escherichia coli</i>.","authors":"Hina Khalid, Sergey Shityakov","doi":"10.1007/s40203-024-00288-z","DOIUrl":"10.1007/s40203-024-00288-z","url":null,"abstract":"<p><p>Urinary tract infections (UTIs), largely caused by uropathogenic <i>Escherichia coli</i> (UPEC), are increasingly resistant to antibiotics and frequently recur. Using immunoinformatics, we designed a multiepitope peptide vaccine targeting UPEC virulence factors, including iron acquisition systems and adhesins. The construct features 12 cytotoxic T lymphocyte epitopes, six helper T lymphocyte epitopes, and six B-cell epitopes,and isoptimized for high antigenicity, immunogenicity, nontoxic, and low allergenic potential. Molecular docking and 0.4-µs molecular dynamics simulations revealed the molecular mechanism of theinteraction of the vaccine with Toll-like receptor 4 and a favorable binding energy of - 41.83 kcal/mol using an implicit solvation model. These promising in silico results suggest the potential efficacy of the vaccine in preventing UPEC infections and underscore immunoinformatics as a powerful tool for addressing antibiotic-resistant UTI pathogens.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00288-z.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883681","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":"Virtual screening and molecular dynamics studies of novel small molecules targeting <i>Schistosoma mansoni</i> DHODH: identification of potential inhibitors.","authors":"Saudatu Chinade Ja'afaru, Adamu Uzairu, Vipin Kumar Mishra, Muhammed Sani Sallau, Muhammad Tukur Ibrahim, Amit Dubey","doi":"10.1007/s40203-024-00281-6","DOIUrl":"https://doi.org/10.1007/s40203-024-00281-6","url":null,"abstract":"<p><p>Schistosomiasis affects more than 200 million individuals globally, mainly in underprivileged areas, leading to long-term health issues and adding to socio-economic challenges. The existing reliance on a solitary medication (Praziquantel) gives rise to concerns about drug resistance and possible side effects. The exploration of alternative treatments is crucial to meet the demand for more efficient, safer, and cost-effective remedies, guaranteeing continuous control and eradication initiatives while reducing the risk of drug resistance. To address these issues, we employed a structure-based drug design approach, generating eighteen innovative inhibitors targeting <i>Schistosoma mansoni</i> Dihydroorotate dehydrogenase (SmDHODH). A robust QSAR model yielded promising statistical parameters, and molecular docking of 31 known inhibitors lead to the identification of a lead candidate (Compound <b>21</b>) with favorable binding efficacy. Eighteen novel compounds were designed, showing improved binding affinities compared to both the lead compound and the standard drug, Praziquantel (PZQ). Molecular dynamics simulations and Density Functional Theory (DFT) affirmed the reactivity and stability of protein-ligand complexes under physiological conditions. These compounds exhibit strong inhibition of SmDHODH and meet drug-likeness criteria. Additionally, they demonstrate favorable pharmacokinetic properties, suggesting their potential effectiveness in treating schistosomiasis. Our study underscores the importance of understanding molecular properties for optimizing treatments against this neglected tropical disease.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00281-6.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"113"},"PeriodicalIF":0.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775989","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 telomeric RNA quadruplexes with natural metabolites to prevent cancer.","authors":"Gourav Choudhir, Sushil Kumar, Anuj Kumar","doi":"10.1007/s40203-024-00283-4","DOIUrl":"10.1007/s40203-024-00283-4","url":null,"abstract":"<p><p>Cancer is a major global health burden, causing significant economic losses and premature deaths worldwide. Maintenance of telomeric repeats by telomerase makes the cancer cells immortal. Non-nucleoside mushroom metabolites were screened for their ability to stabilize RG4 structures, making telomeres inaccessible to telomerase and inducing telomere shortening in cancer cells. Selected mushroom metabolites, namely, Sterenin M, Melleolide K, and Zhankuic Acid A were docked with RG4 using the AutoDock Vina and evaluated for non-covalent interactions. These compounds were found to have strong binding affinity and manifested a set of molecular interactions with RG4. To assess the stability of complexes, state-of-the-art molecular dynamics simulations were carried out using the GROMACS 2018.7 software suite with the AMBER99SB-ILDN force field on 250 nanoseconds. Molecular docking and MD simulations revealed the strong interaction patterns between RG4 and the selected metabolites at the atomic level followed by binding free energy calculations. The results suggest that all three metabolites have the potential to be developed into therapeutic agents for cancer treatment. Further in vitro and in vivo studies are needed to assess these compounds' toxicity, efficacy, and dosage.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"112"},"PeriodicalIF":0.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752718","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":"Investigating the antibacterial potential of thiophene derivatives against wound infections: a combined DFT, molecular docking, and ADMET study targeting <i>Staphylococcus aureus, Pseudomonas aeruginosa,</i> and <i>Escherichia coli</i> resistant genes.","authors":"Mathias O Ajaba, Bassey E Agbo, Nse Umoh, Ekaette S Udoh, Alpha O Gulack, Andrew Ushie, Friday O Izachi, Bethel C Ateb","doi":"10.1007/s40203-024-00279-0","DOIUrl":"10.1007/s40203-024-00279-0","url":null,"abstract":"<p><p>Wound infection poses a significant global health threat, as it is a leading cause of morbidity and mortality among surgical patients and individuals with burn injuries, resulting in substantial healthcare burdens and devastating outcomes worldwide. <i>Staphylococcus aureus</i>, <i>Pseudomonas aeruginosa</i>, and <i>Escherichia coli</i> have frequently been implicated as major pathogens causing wound infections. This has eventually and consistently given rise to antimicrobial resistance divulging a need to mitigate infectious outbreaks. Herein, we employed a computational density functional theory (DFT) method at ωB97XD/6-311++g(d, p) level of theory to evaluate the performance of the thiophene derivative 5-(4-bromo-5-(methylthio)thiophen-2-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol 4, which is experimentally synthesized into five compounds (4a, 4b, 4c, 4d, and 4e). The chemical reactivity, kinetic stability, nature of interactions and functional characteristics of the thiophene derivatives were ascertained. The resistance gene PDB ID: 1K25, 2D45, 4UOT, and 7K2X were employed and docked with thiophene derivatives. Interestingly, molecular docking analysis demonstrated that ligands 4a, 4b, 4c, 4d, and 4e are more effective against proteins 1K25, 4U0T and 7K2X than amoxicillin and methicillin. Upon docking with the 2D45 protein, compounds 4c and 4e (- 5.9 kcal/mol) exhibited potential similar to that of methicillin (- 5.9 kcal/mol), while 4a and 4b showed slightly better affinities (- 6.1 kcal/mol and 6.0 kcal/mol). Using Lipinski's Rule of Five (Ghose filter, Veber rules, Muegge filter, and Egan's rule), 4d and 4e were determined to be the most promising candidates for drug development due to their compliance with all evaluated criteria, indicating favourable properties for oral bioavailability and drug likeness. This research suggested that thiophene derivatives can serve as promising antibacterial agents against wound-infected bacteria.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"111"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712323","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":"Bioactive compounds from fermented <i>Vernonia amygdalina</i> leaf: Potent antibiotics against multidrug-resistant <i>Escherichia coli</i> and <i>Salmonella typhi</i>.","authors":"Adeleke Kazeem Atunnise, Ibukun Temitope Sossou, Peace Sekani Peters, Solomon Damilare Ajayi, Dumebi Anthony Elechukwu, TiOluwani Bamdele Salau, Olusegun Lateef Adebayo, Bamidele Adewale Salau","doi":"10.1007/s40203-024-00277-2","DOIUrl":"10.1007/s40203-024-00277-2","url":null,"abstract":"<p><p>Antibiotic resistance microorganisms (ARMs), particularly gram-negative bacteria, pose a global health threat. The effects of fermentation on phytochemicals are numerous, and exploring this potential is the focus of drug development. The study investigated the role of fermentation in modifying <i>V. amygdalina</i> leaf secondary metabolites as an effective antibiotic against <i>Escherichia. coli, Bacillus subtilis and Salmonella typhi</i>. This work showed that fermentation increased the content of lycopene, flavonoid and carotenoid compounds but decreased chlorophyll, soluble protein and phenol. Pearson's correlation <i>heatmap</i> showed a strong correlation between microbial activities and secondary metabolic changes. The methanolic extract of fermented <i>V. amygdalina</i> leaf pulp (at day 9) showed significant antioxidant and anti-inflammatory activities. The GCMS and FTIR results showed unique compounds and structural modifications at different intervals of the fermentation period. <i>In-vitro and in-silico</i> analyses showed that fermentation did not alter the inhibition rate against <i>B. subtilis;</i> however, <i>E. coli and S. typhi</i> were significantly inhibited by fermented V. amygdalina pulp extracts. <i>In-silico</i> analyses showed that 4,6-Cholestadien-3β-ol- a compound present only on the ninth day of fermentation-was responsible for the inhibition of the gram-negative bacteria via the substitution of multiple non-ionic interactions of some key catalytic site residues with non-ionic types, thereby denying ionisation and salt-bridge properties that porins explore to resist antibiotics; and higher binding affinity to OmpC and OmpF than ampicillin. Therefore, this steroid-derived compound may open a new pipeline for developing ion-independent multi-target antibiotics against broad-spectrum multidrug-resistant gram-positive and gram-negative bacteria in food and pharmaceutical purposes.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00277-2.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"106"},"PeriodicalIF":0.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683849","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 studies on evaluating the liver-protective effectiveness of a polyherbal formulation in preventing hepatocellular carcinoma progression.","authors":"Haritha Kalath, Riya Vishwakarma, Bhavya Banjan, Krishnapriya Ramakrishnan, Abel John Koshy, Rajesh Raju, Niyas Rehman, Amjesh Revikumar","doi":"10.1007/s40203-024-00285-2","DOIUrl":"10.1007/s40203-024-00285-2","url":null,"abstract":"<p><p>Liv-52, an herbal formulation consisting of seven distinct plants and Mandur Bhasma, is recognized for its hepatoprotective, anti-inflammatory, and antioxidant properties. To investigate the pharmacological potential of each phytochemical from these plants, we conducted ADMET analysis, molecular docking, and molecular dynamic simulations to identify potent molecules capable of inhibiting the interaction between Alpha-fetoprotein (AFP) and Cysteine aspartyl protease 3 (Caspase-3/CASP3). In our study, we have used molecular docking of all the compounds against AFP and filtered them on the basis of ADME properties. Among the compounds analyzed, (-) Syringaresinol from <i>Solanum nigrum</i>, exhibited good binding interactions with AFP, the highest binding free energy, and maintained stability throughout the simulation along with favorable drug likeness properties based on ADME and Toxicity analysis. These findings have strongly indicated that (-) Syringaresinol is a potential inhibitor of AFP, providing a promising therapeutic avenue for hepatocellular carcinoma (HCC) treatment by inhibiting the interaction between AFP and CASP3, thereby reinstating normal CASP3 activity. Further in vitro studies are imperative to validate the therapeutic efficacy of (-) Syringaresinol as an AFP inhibitor, potentially impeding the progression of HCC.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00285-2.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"109"},"PeriodicalIF":0.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683974","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}