Autodock Vina Research Articles

Antiangiogenic potential of Elaeagnus umbellata extracts and molecular docking study by targeting VEGFR-2 pathway

Abstract Background Anti-angiogenesis or inhibition of blood vessel formation is the best way to prevent the growth and metastasis of tumors. Natural sources like plants are currently being explored for its antiangiogenic activity as they are factories of various phytochemicals. The goal of the current study is to investigate the antiangiogenic potential of Elaeagnus umbellata (E. umbellata) by using chorioallantoic membrane (CAM) assay and molecular docking. Methods Based on our previous research, the antiangiogenic activity was carried out using active fractions including crude methanol (Eu-Met), ethyl acetate (Eu-EtAc), and chloroform (Eu-Chf) extracts using CAM assay. Furthermore, to understand the binding mechanism of identified compounds, molecular docking was performed against vascular endothelial growth factor receptor 2 (VEGFR-2) using AutoDock vina as docking software. VEGFR-2 is overexpressed in pathological angiogenesis. Results In CAM assay, Eu-Met, Eu-EtAc, and Eu-Chf extracts showed antiangiogenic activities but notable antiangiogenic activities were exhibited by Eu-Chf with IC50 value of 65.02 μg/mL. In molecular docking, five compounds, catechin, catechin hydrate, morin, quercetin, and rutin, reported in the extract and active fractions (Eu-Met, Eu-EtAc, and Eu-Chf) of E. umbellata showed strong interactions with VEGFR-2 with binding affinities of −9.4, −9.3, −9.9, −10.2, and −9.4 kcal/mol. Conclusion Based on our results, we can claim that E. umbellata possess antiangiogenic activity which needs to be explored further.

Unraveling the potential of Epicatechin gallate from crataegus oxyacantha in targeting aberrant cardiac Ca2+ signalling proteins: an in-depth in-silico investigation for heart failure therapy

The cardiovascular sarcoplasmic reticulum (SR) calcium (Ca2+) ATPase is an imperative determinant of cardiac functionality. In addition, anomalies in Ca2+ handling protein and atypical energy metabolism are inherent in heart failure (HF). Moreover, Ca2+ overload in SR leads to mitochondrial matrix Ca2+ overload, which can trigger the generation of Reactive Oxygen Species (ROS), culminating in the triggering of the Permeability Transition Pore (PTP) and Cytochrome C release, resulting in apoptosis that leads to arrhythmias and numerous disorders. Although proteins involved in the molecular mechanism of Ca2+ dysfunction regarding mitochondrial dysfunction remains elusive, this study aims to assess the major Ca2+ handling proteins which may be involved in the Ca2+ malfunction that causes mitochondrial dysfunction and predicting the most effective drug by targeting the analyzed Ca2+ handling proteins through various insilico analyses. Thirteen proteins absorbed from interaction analysis were docked with four optimal phytochemicals from Crataegus oxyacantha (COC). Furthermore, The ADME profile of tyramine, vitexin, Epicatechin, and Epicatechin gallate was acclimated to evaluate potential drugability utilizing QikProp. So, molecular docking evaluations were performed using Glide (Maestro), autodock, and vina. Based on the results of 156 dockings by Maestro, auto-dock, and auto-dock vina, PKAC-a with Epicatechin gallate exhibits good interaction. Therefore, a 2000 ns molecular dynamics (MD) simulation was utilized to assess the feasible phytochemical Epicatechin gallate - PKAC-a complex binding stability utilizing Desmond and this study confirmed that Epicatechin gallate from COC has high possibilities to inhibit the aberrant cardiac Ca2+ signaling proteins due to its conformational rigidity.

Validating anti-inflammatory and cytotoxic properties of Fagonia cretica L. through metabolic, in vitro, and in silico profiling

BackgroundFagonia cretica L. (Family: Zygophyllaceae), is a wild shrub mostly found in Mediterranean districts and extensively used in folk medicine for a vast array of purposes such as antidiabetic and anticancer during the early stages. The goal of the current study was to validate the antioxidant, anti-inflammatory, and cytotoxic properties of Egyptian F. cretica using in vitro studies, metabolic profiling, and in silico approaches.MethodsThe plant was collected from the Egyptian desert and the alcoholic extract was prepared from its aerial parts, total phenolic and total flavonoid contents were evaluated spectrophotometrically. Antioxidant potential was assessed via 1,1 diphenyl-2-picrylhydrazyl (DPPH) scavenging activity. Anti-inflammatory activity was validated through in vitro COX-2, COX-1, and nitric oxide inhibition. Cytotoxicity was tested against liver (HepG2), breast (MCF-7), and intestinal (CACO2) carcinoma cell lines followed by assessment of its impact on the levels of apoptotic markers namely topoisomerase I and caspase 9 enzymes. Chemical profiling of the extract was performed using LC-HRMS technique. Saponin rich extract was prepared and tested for affecting topo I and caspase 9 enzymes. In silico studies were conducted on anti-inflammatory (COX-2 and COX-1) and cytotoxicity (topoisomerases I, IIα, and IIβ) targets using Autodock vina in PyRx platform.ResultsTotal phenolic and total flavonoid content of the extract were 2.4 ± 0.12 mg GAE/g and 0.18 ± 0.01 mg RE/g, respectively. In vitro results revealed antioxidant activity calculated as 1.4 ± 0.1 mg AEAC/g. In vitro anti-inflammatory assays unveiled inhibition of COX-2 and COX-1 enzymes with IC50 values of 13.02 ± 0.61 and 26.51 ± 0.83 µg/ml, respectively and nitric oxide with IC50 of 147.05 ± 9.61 µg/ml. Cytotoxicity on MCF-7, HepG2, and CACO2 cell line with IC50 values of 6.9 ± 0.53, 7.6 ± 0.42, and 9.2 ± 0.35 µg/ml, respectively, in addition to in vitro topoisomerase I inhibition (IC50 = 13.57 ± 0.71 µg/ml) and caspase 9 induction by 5.66 folds. Metabolic profiling using LC-HRMS technique resulted in dereplication of 21 compounds including triterpenoid saponins, flavonoids, diterpenoids, etc. Interestingly, saponin rich fraction and non-saponin fraction exhibited similar effects on topoisomerase I and caspase 9. In silico investigation unveiled high binding affinities of almost all the detected metabolites to the active sites of COX-2, COX-1, topo I, IIα, and IIβ enzymes.ConclusionCollectively, we can conclude that F. cretica is a new source of many phytochemicals, and a significant natural source as cytotoxic and anti-inflammatory agent.

<b>In Silico Studies as Support for Natural Products Research</b>

It can be argued that in silico studies do not receive enough attention despite being a key part of addressing the limitations of our laboratory facilities, the high cost of chemicals, and the equipment required for wet laboratory activities. Natural product studies are demanding higher costs of chemicals, reagents, and varied laboratory facilities. This becomes a serious limitation in getting data from natural product studies. In silico studies use chemical structures as inputs as well as software and online web servers to generate data to support, predict, and validate wet laboratory activities. Interaction studies use computational tools to calculate binding energies and other associated properties. Predictions are based on the structure-activity relationships derived from previously conducted preclinical and clinical studies. As a main component of in silico studies, the physicochemical and pharmacokinetic properties of small molecules can be determined using online web servers such as SwissADME and ADMET web servers. An interaction study uses molecular docking software such as AutoDock, AutoDock vina, GOLD, and online servers such as SwissDock. Furthermore, the stabilities of complexes considered in interaction studies can be confirmed using molecular dynamics simulation software such as VMD. Prediction of activity spectra for substances (PASS) is widely used to predict biological activities for molecules based on MNA descriptors. In silico studies have played an important role in medicinal chemistry, pharmacology, and related research for screening, interaction studies, prediction, and other related purposes. Results of in silico predictions will not be far from wet lab activities as in most cases these studies consider previously attempted clinical and preclinical biological activities. Some examples are presented here to encourage the use of in silico studies. Received: 15 July 2024 | Revised: 27 August 2024 | Accepted: 25 Ocotber 2025 Conflicts of Interest The authors declare that they have no conflicts of interest to this work. Data Availability Statement The data that support this work are available upon reasonable request to the corresponding author. Author Contribution Statement Fekade Beshah Tessema: Conceptualization, Methodology, Writing - original draft, Visualization. Tilahun Belayneh Asfaw: Validation, Writing - review & editing. Mesfin Getachew Tadesse: Resources, Visualization, Supervision. Yilma Hunde Gonfa: Validation, Writing - review & editing. Rakesh Kumar Bachheti: Resources, Visualization, Supervision.

Influence of Pyridine Entangled Novel Hybrid Quinoxaline Spirane on the Fluorescence and Absorption Spectra of Biomolecules: Molecular Docking, Pharmacokinetic, and In-Vitro Biological Investigations.

Spectroanalytical techniques are extensively employed in contemporary research to characterize compounds and assess their biological activity. The β-lactam ring containing twenty novel spiro quinoxaline-pyridine heterocyclic compounds (A - T) were synthesized and characterized using 1H NMR, 13C NMR, FT-IR, and mass spectrometry. The compounds must interact with DNA to adequately assess their potential anticancer action. Thus, their binding affinities with calf-thymus (CT) DNA and bovine serum albumin (BSA) were evaluated using a UV-visible spectrophotometer. The Kb value of compound-DNA and compound-BSA was found in the order of 0.51-2.53 M- 1 and 0.11-2.03 M- 1, respectively. Furthermore, a fluorescence quenching study was also carried out using a fluorescence spectrometer to explore DNA/BSA binding, and a partial intercalation type of binding was suggested. MTT assay was performed to evaluate the anticancer activity of the compounds. A docking study of all the compounds was performed with DNA (1 BNA), BSA (4F5S), and topoisomerase II (3QX3) using autodock vina software. SwissADME and admetSAR, two online platforms, were used to assess the pharmacokinetic profile and determine the drug-likeness of the synthesized compounds.

Exploring Natural Compounds Targeting the Bacterial SHV Protein to Combat Antibiotic Resistance: A Biocomputational Study

Background: Antibiotic-resistant (AR) bacteria are rapidly spreading worldwide, posing a serious threat to antibiotic efficacy. Bacterial infections have emerged as a persistent threat following decades of antibiotic use. Sulfhydryl variable (SHV) is a well-known bacterial enzyme linked to AR. SHV has a high degree of genetic diversity, resulting in the existence of numerous distinct variants. Methods: The PyRx AutoDock VINA was used to conduct in-silico screening of a natural compound library to assess their interaction with the SHV-1 protein. SwissADME web tools were used to predict the physicochemical, drug-likeness, and ADMET properties of the selected compounds.Result: The compounds PSCdb00708, PSCdb00149, PSCdb00698, and PSCdb00175 bind strongly to the SHV-1 protein and interact strongly with the SHV-1 active site residues, as well as having several amino acid residue interactions in common with avibactam. These compounds exhibited higher binding affinity values than avibactam. Furthermore, these compounds demonstrated no violation of drug-likeness.Conclusion: The compounds PSCdb00708, PSCdb00149, PSCdb00698, and PSCdb00175 can be employed as SHV-1 inhibitors in the management of AR. However, experimental validation is required to optimize them as SHV-1 inhibitors.Keywords: Antibiotic-resistant; Antibiotic; Virtual screening; AutoDock; SHV-1 protein

Amalgamated Pharmacoinformatics Study to Investigate the Mechanism of Xiao Jianzhong Tang against Chronic Atrophic Gastritis.

Traditional Chinese medicine (TCM) Xiao Jianzhong Tang (XJZ) has a favorable efficacy in the treatment of chronic atrophic gastritis (CAG). However, its pharmacological mechanism has not been fully explained. The purpose of this study was to find the potential mechanism of XJZ in the treatment of CAG using pharmacocoinformatics approaches. Network pharmacology was used to screen out the key compounds and key targets, MODELLER and GNNRefine were used to repair and refine proteins, Autodock vina was employed to perform molecular docking, Δ Lin_F9XGB was used to score the docking results, and Gromacs was used to perform molecular dynamics simulations (MD). Kaempferol, licochalcone A, and naringenin, were obtained as key compounds, while AKT1, MAPK1, MAPK14, RELA, STAT1, and STAT3 were acquired as key targets. Among docking results, 12 complexes scored greater than five. They were run for 50ns MD. The free binding energy of AKT1-licochalcone A and MAPK1-licochalcone A was less than -15 kcal/mol and AKT1-naringenin and STAT3-licochalcone A was less than -9 kcal/mol. These complexes were crucial in XJZ treating CAG. Our findings suggest that licochalcone A could act on AKT1, MAPK1, and STAT3, and naringenin could act on AKT1 to play the potential therapeutic effect on CAG. The work also provides a powerful approach to interpreting the complex mechanism of TCM through the amalgamation of network pharmacology, deep learning-based protein refinement, molecular docking, machine learning-based binding affinity estimation, MD simulations, and MM-PBSA-based estimation of binding free energy.

Experimental and Theoretical Studies for Noncovalent Interactions Analysis of 2-Phenyl Imidazole Derivative: Perspective for Anti-Inflammatory Activity

Synthesis of 2-Phenyl imidazole derivative has been carried out for the studies of quantitative non-covalent interactions and anti-inflammatory activity. Hirshfeld surface analysis, crystal structure, and non-covalent interaction computation have all been used to do quantitative investigations of non-covalent interactions. The intermolecular interactions calculations have been done with crystalexplorer 17. Further, anti-inflammatory activities of synthesized molecules were evaluated by molecular docking studies through autodock vina and in-vivo studies through carrageenan rat model. The molecular docking and in-vivo studies revealed that all molecules have shown significant anti-inflammatory activity, compared to standard drugs nimesulide.

DRUGGABILITY AND MOLECULAR DOCKING OF ESSENTIAL SECONDARY METABOLITES FROM Azadirachta indica LEAF AGAINST ANGIOTENSIN CONVERTING ENZYME-2: COVID-19 IN FOCUS

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious and virulent coronavirus that arose in late 2019 and poses great risk to public health and safety. The SARS-CoV-2 utilizes peptidase, angiotensin-converting enzyme 2 (ACE2) for entrance and invasion into host cells. Thus, this study explored the in-silico druggability and molecular docking of essential secondary metabolites (ESMs) from Azadirachta indica leaf as potential inhibitors of ACE-2, a main receptor for the SARS-CoV-2 virus causing the COVID-19 pandemic. Through a literature survey and database mining of known compounds from A. indica in the National Center for Biotechnology Information (NCBI) database, 12 secondary metabolites and 5 FDA COVID-19-approved drugs were identified. The in-silico druggability and molecular docking experiments were performed using SwissADME and ADMETlab tools, and Autodock vina and UCSF Chimera respectively. Discovery Studio was used for docking visualization and analyses of ligand-target interactions. The results suggest potential candidates for further consideration. Of the 12 secondary metabolites from A. indica and 5 FDA-approved drugs identified, azadirachtin A, azadirachtin D, azadirachtin H, azadirachtin F, azadirachtin I and nimbolin, and ivermectin showed relatively poor druggability. Of the 5 FDA-approved medications for the treatment of COVID-19 under investigation, only paritaprevir was able to dock (representing 20%); while 6 out of the 12 compounds from A. indica were able to dock perfectly (representing 50%). The best docking results identified paritaprevir, desacetylnimbin, azadiradione, nimbin, nimbolide, nimbinene, and azadirone as capable of binding to ACE-2 with the lowest free energy (binding score) of -14.60, -11.88, -11.60, -12.33, -12.78, -12.58, and -11.40 kcal/mol respectively. This study indicated that desacetylnimbin, azadiradione, nimbin, nimbolide, nimbinene, and azadirone from A. indica leaf are potent inhibitors of hACE2 with high druggability potentials. Hence, they are valuable natural bioactive compounds capable of targeting ACE-2 as potential therapeutics against the SARS-CoV-2 virus causing COVID-19.

Identification of novel natural compounds against CFTR p.Gly628Arg pathogenic variant

Cystic fibrosis transmembrane conductance regulator (CFTR) protein is an ion channel found in numerous epithelia and controls the flow of water and salt across the epithelium. The aim of our study to find natural compounds that can improve lung function for people with cystic fibrosis (CF) caused by the p.Gly628Arg (rs397508316) mutation of CFTR protein. The sequence of CFTR protein as a target structure was retrieved from UniProt and PDB database. The ligands that included Armepavine, Osthole, Curcumin, Plumbagine, Quercetin, and one Trikafta (R*) reference drug were screened out from PubChem database. Autodock vina software carried out docking, and binding energies between the drug and the target were included using docking-score. The following tools examined binding energy, interaction, stability, toxicity, and visualize protein-ligand complexes. The compounds having binding energies of −6.4, −5.1, −6.6, −5.1, and − 6.5 kcal/mol for Armepavine, Osthole, Curcumin, Plumbagine, Quercetin, and R*-drug, respectively with mutated CFTR (Gly628Arg) structure were chosen as the most promising ligands. The ligands bind to the mutated CFTR protein structure active sites in hydrophobic bonds, hydrogen bonds, and electrostatic interactions. According to ADMET analyses, the ligands Armepavine and Quercetin also displayed good pharmacokinetic and toxicity characteristics. An MD simulation for 200 ns was also established to ensure that Armepavine and Quercetin ligands attached to the target protein favorably and dynamically, and that protein-ligand complex stability was maintained. It is concluded that Armepavine and Quercetin have stronger capacity to inhibit the effect of mutated CFTR protein through improved trafficking and restoration of original function.

In silico Design of a Quadruplex RNA Aptamer Against Carcinoembryonic Antigen, and Evaluating its Potential as a Drug Delivery Vehicle

Background: Colorectal cancer is the third most common cancer worldwide, with carcinoembryonic antigen (CEA) being a key biomarker for tumor prognostic assessment. This study focused on the in silico development of an RNA aptamer capable of efficiently targeting the CEA biomarker, and evaluating its potential to act as a drug delivery vehicle of chemotherapeutic anticancer drugs. Methods: In this study, five G-quadruplex RNA aptamers were manually designed and docked with the CEA protein. The aptamer sequence with the best docking score was optimized through various mutations, and these mutant sequences underwent drug-aptamer docking using AutoDock vina, followed by further docking experiments with CEA, with and without the drug, using the Hdock server. The best aptamer-drug configuration and the entire (aptamers-drug)-CEA complex were then analyzed using molecular dynamics (MD) simulation. Results: Irinotecan exhibited the highest binding affinity with three mutant sequences compared to 5-FU and Raltitrexed, with the seq 3-5/Irinotecan complex showing the best configuration (score: -11.6). This complex also demonstrated a good binding affinity with the target CEA (HDOCK score: -393.07). Throughout 31.6 ns simulation, the RMSD plot of the (aptamer-drug)-CEA complex showed an average of 8.7 A°. The residues of interacting amino acids had lower RMSF than 1.4 Å, except for the ALA A0 (RMSF:1.74 Å). Rg plot showed minimal fluctuation, which were maintained between 19.2 Å and 20.2 Å. The mean SASA was in the range of 112.8–125.8 nm2. H-bonds were observed with an average of 7.3 hydrogen bonds. MD simulation results indicated that the (aptamers-drug)-CEA complex maintained a stable, low-flexibility, and relatively compact structure throughout the simulation. Conclusion: The study concludes that the designed quadruplex RNA aptamer can potentially target the CEA biomarker with good binding affinity and serves as an effective carrier for Irinotecan. However, in vitro and in vivo experiments are necessary for further validation.

Exploring Juniperus phoenicea L extract through phytochemical analysis, anti-lipase effects, and comprehensive molecular studies

Lipase inhibitors are used in the treatment of candidiasis, obesity, and acne problems. Therefore, the investigation of new natural lipase inhibitors has generated great interest. Juniperus phoenicea is a small Mediterranean tree considered an important medicinal plant. Through this work, we investigated the composition and inhibition effect of J. phoenicea extract on Candida rugosa and human lipases; and we analyzed the interactions between detected compounds and lipases using molecular docking, ADME-T, and dynamic studies. We extracted the secondary metabolites from the plant aerial parts and tested their activities against lipase. We examined major components of J. phoenicea, using Autodock vina for molecular docking, Desmond from Schrodinger suite 2021–1 for dynamics, and evaluating its drug-likeness and toxicity properties using ADMET webserver. We found that the IC50 values of ethyl acetate and methanol extracts are 1.33±0.10 and 1.731 mg/mL. Using HPLC quantitative analysis we identified in ethyl acetate extract the following phenolic compounds gallic acid, rutin, apigenin-7-O-glucoside, cinnamic acid, and quercetin. The complex apigenin-7-O-glucoside-lipase is stabilized by four hydrogen bonds and hydrophobic interactions, and the binding energy equals -10 Kcal/mol, which is better than the interactions saved for orlistat. Dynamic Simulation demonstrated better stability in the ligand-protein complex apigenin-7-O-glucoside-1lpb within 100 ns than the orlistat-1lpb complex. This study is described in this work for the first time. The results indicated that apigenin-7-O-glucoside from J. phoenicea L could be a good choice to develop a new drug candidate against candidiasis, obesity, and other lipase-related diseases.

Investigation of substituent effects on the electronic structure and antiviral activity of favipiravir derivatives for Covid-19 treatment using DFT and molecular docking

In this study, Density-functional theory/Time-dependent density-functional theory (DFT/TDDFT) and Molecular docking method was used to investigate the effect of methyl acetate, tetrahydrofuran and cyanobenzylidene substituents on the electronic structure and antiviral activity of favipiravir for treating COVID-19. The DFT and TDDFT computations were employed using the Gaussian 09 software package. The values were calculated using the 6-311++G(d, p) basis set and the hybrid B3LYP functional method. Autodock vina software was used for simulations to better predictions and to validate the modified compounds' binding affinities and poses. Results of the study indicate that compounds 1 to 6 all displayed a planar structure, where the pyrazine ring, carboxamide, hydroxyl groups, and other substituents are all situated within the same plane. In addition, the energy gaps (Egap) of these six compounds (Cpd 1, 2, 3, 4, 5, and 6) were compared. The significant dipole moment and binding affinity achieved implies a particular orientation for binding within the target protein, signaling the anticipated strength of the binding interaction. In all six compounds, the electrophilic domain is situated in the vicinity of the amine functional group within the carboxamide compound, whereas the nucleophilic domain encompasses both the carbonyl and hydroxyl groups. The most negatively charged sites are susceptible to electrophilic interactions. In conclusion, compounds 5 and 6 exhibit a high binding affinity of the target protein, while compound 6 has a high energy gap, which could enhance its antiviral activity against the COVID-19 virus.

Rosolic acid as a novel activator of the Nrf2/ARE pathway in arsenic-induced male reproductive toxicity: An in silico study

Male reproductive toxicity as a result of arsenic exposure is linked with oxidative stress and excessive generation of reactive oxygen species (ROS). It leads to an imbalance between ROS production and antioxidant defense mechanisms ultimately resulting in male infertility. The nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) is a transcription factor that responds to cellular stressors controlling the oxidative state, mitochondrial dysfunction, inflammation, and proteostasis. This study aims to investigate the potential of Rosolic acid (ROA) to act as a novel Nrf2 activator by mitigating oxidative stress to combat arsenic-induced male reproductive toxicity. The protein and ligands were prepared in the BIOVIA Discovery Studio, followed by protein-ligand docking using auto dock vina integrated with the PyRx-Virtual Screening Tool. Then the ADME properties were analyzed using the SwissADME tool to get a clear idea about the physicochemical properties, lipophilicity, water solubility, pharmacokinetics, and drug likeliness of ROA. It was followed by molecular dynamics simulation (MDS) studies using GROMACS. The 3D and 2D interaction maps revealed the interactions of Keap 1 with ROA. Keap1-ROA complex was found to have a binding energy of −7.8 kcal/mol. ROA showed 0 violations for Lipinski and 0 alerts each for PAINS and Brenk and a bioavailability score of 0.55. The BOILED-Egg representation showcases that ROA is predicted as passively crossing the blood-brain barrier (BBB). The MDS described 2FLU-ROA as a stable system. This work portrays that ROA can be a potent Nrf2 activator by exhibiting an inhibitory activity against the Keap1 protein and thus mitigating oxidative stress in arsenic-induced male reproductive toxicity.

In vitro cytotoxic activity of chemically synthesized ZnTe nanoparticles against human lung cancer cell line L-132 with supported molecular docking study

Among all the cancer cases, Lung cancer is the most common worldwide, which needs more potential therapy. But there are many limitations in the present therapy used for lung cancer treatment. Recently, many researchers are using different types of nanoparticles as an alternative for this purpose. Here, with such interest, ZnTe nanocrystals have been synthesized using a wet-chemical method, which is a cost-effective and easy method. After preparing the ZnTe nanocrystals, morphology has been analyzed through a scanning electron microscope (SEM) and the crystallinity of the prepared ZnTe nanocrystals has been investigated using X-ray diffraction analysis. After that, cytotoxicity of the prepared ZnTe nanoparticles has been examined at three different concentrations (100 ng/ml, 1 μg/ml, 100 μg/ml) on human lung cancer cell line L-132 using the MTT assay. From the experimental results, it is observed that a batter percentage of about 56 % of killing has been obtained at the concentration of 100 μg/ml after 24 h of treatment. It may happen that ZnTe nanoparticles enter through the cell membrane and induce cell apoptosis. For better understanding, molecular docking has been performed using ‘auto dock vina’ to find the binding confirmation of ZnTe nanoparticles with the lung cancer cell line L-132. Both the biological and computational methods confirm that nanocrystalline ZnTe is a therapeutic candidate for the treatment of lung cancer cells.

Network pharmacology and experimental validation to explore the role and potential mechanism of Liuwei Dihuang Decoction in prostate cancer

ObjectiveTo evaluate the anti-tumor effector of Liuwei Dihuang Decoction (LWDHD) in prostate cancer (PCa) and explore the potential mechanism using experimental validation, network pharmacology, bioinformatics analysis, and molecular docking.MethodsCCK test, Clone formation assay and wound-healing assays were used to determine the effect of LWDHD on prostate cancer growth and metastasis. The active ingredients and targets of LWDHD were obtained from the TCMSP database, and the relevant targets were selected by GeneCards, OMIM and DisGeNET databases for PCa. The cross-targets of drugs and disease were imported into the STRING database to construct protein interactions. The network was also visualized using Cytoscape software and core targets are screened using the Network Analyzer plug-in. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed using R software. TCGA database was used to analyze the correlation of bioinformatics genes. AutoDock vina was used to predict the molecular docking and binding ability of active ingredients to key targets. Through WB and q-PCR experiments, the above gene targets were detected to verify the effect of LWDHD on PCa.ResultsCCK and scratch tests confirmed that LWDHD could inhibit the proliferation, invasion and migration of prostate cancer cells. Clone formation experiments showed that LWDHD inhibited the long-term proliferative capacity of PC3 cells. LWDHD and PCa had a total of 99 common targets, establishing a “drug-ingredient-common target” network. Through GO and KEGG enrichment analysis, PI3K/AKT, MAPK, TP53 pathway, MYC, TNF pathway and other signaling pathways were found. Bioinformatics analysis showed that MYC gene was highly expressed and CCND1 and MAPK1 were low expressed in prostate cancer tissues. In addition, TP53, AKT1, MYC, TNF and CCND1 were positively correlated with MAPK1, among which AKT1 and CCND1 were most closely correlated with MAPK1. Molecular docking results showed that quercetin, kaempferol, β-sitosterol and other main active ingredients of LWDHD treatment for PCa were combined with core proteins MAPK1 and AKT1 well. WB and q-PCR results showed that LWDHD inhibited the expression of PI3K and AKT in PC3 cells.ConclusionThe mechanism of LWDHD therapy for PCa is a multi-target and multi-pathway complex process, which may be related to the biological processes mediated by MAPK1 and AKT1 pathways, such as cell proliferation and inhibition of metastasis, and the regulation of signaling pathways. The PI3K/AKT signaling pathway may be a central pathway of LWDHD to inhibit prostate cancer proliferation.

Identification of diagnostic signature and immune infiltration for ischemic cardiomyopathy based on cuproptosis-related genes through bioinformatics analysis and experimental validation

BackgroundIschemic cardiomyopathy (IC) is primarily due to long-term ischemia/hypoxia of the coronary arteries, leading to impaired cardiac contractile or diastolic function. A new form of cell death induced by copper, called “cuproptosis” is related to the development and progression of multiple diseases. The cuproptosis-related gene (CuGs) plays an important role in acute myocardial infarction, while the specific mechanisms of CuGs in ischemic cardiomyopathy remain unclear. MethodsThe expressions of CuGs and their immune characteristics were analyzed with the IC datasets obtained from the Gene Expression Omnibus, namely GSE5406 and GSE57338, identifying core genes associated with IC development. By comparing RF, SVM, GLM and XGB models, the optimal machine learning model was selected. The expression of marker genes was validated based on the GSE57345, GSE48166 and GSE42955 datasets. Construct a CeRNA network based on core genes. Therapeutic chemiacals targeting core genes were acquired using the CTD database, and molecular docking was performed using Autodock vina software. By ligating the left anterior descending (LAD) coronary artery, an IC mouse model is established, and core genes were experimentally validated using Western blot (WB) and immunohistochemistry (IHC) methods. ResultsWe identified 14 CuGs closely associated with the onset of IC. The SVM model exhibited superior discriminative power (AUC = 0.914), with core genes being DLST, ATP7B, FDX1, SLC31A1 and DLAT. Core genes were validated on the GSE42955, GSE48166 and GSE57345 datasets, showing excellent performance (AUC = 0.943, AUC = 0.800, and AUC = 0.932). The CeRNA network consists of 218 nodes and 264 lines, including 5 core diagnostic genes, 52 miRNAs, and 161 lncRNAs. Chemicals predictions indicated 8 chemicals have therapeutic effects on the core diagnostic genes, with benzo(a)pyrene molecular docking showing the highest affinity (-11.3 kcal/mol). Compared to the normal group, the IC group,which was established by LAD ligation, showed a significant decrease in LVEF as indicated by cardiac ultrasound, and increased fibrosis as shown by MASSON staining, WB results suggest increased expression of DLST and ATP7B, and decreased expression of FDX1, SLC31A1 and DLAT in the myocardial ischemic area (p < 0.05), which was also confirmed by IHC in tissue sections. ConclusionIn summary, this study comprehensively revealed that DLST, ATP7B, FDX1, SLC31A1 and DLAT could be identified as potential immunological biomarkers in IC, and validated through an IC mouse model, providing valuable insights for future research into the mechanisms of CuGs and its diagnostic value to IC.

In-vitro Isolation of Serratia marcescens and Computational Analysis of Lipase–Chitinase as a Hybrid Enzyme for the Degradation of Fungicides to Sustain the Ecosystem

The application of fungicides for commercial purposes has grown in response to increased food demand and shifting disease patterns. However, there is a scarcity of studies demonstrating their proper degradation. Due to the expanding global population, there is a heightened need for more agriculture to fulfill the growing demand for food, and this necessitates safeguarding crops from pests and diseases. Disease outbreaks in crops can result in the loss of food and the depletion of valuable resources. According to the European Union, organic fungicides constitute 60% of all fungicide sales, while synthetic fungicides make up the remaining 40% of pesticide sales. Fungicide usage is indispensable but needs to be considered within the context of potential environmental risks. Nonetheless, there is a pressing need to break down fungicides to preserve the natural environment. Our research is centered on hybrid enzymes derived from [Formula: see text] marcescens, which exhibit the capability to degrade fungicides. We employed computational techniques to assess the enzymes’ effectiveness in breaking down fungicides. S. marcescens was isolated from soil and identified through 16s rRNA analysis. Chitanase and lipase, enzymes identified in S. marcescens, can individually break down fungicides, as confirmed by auto-dock vina docking simulations. Notably, the combined action of these two enzymes surpasses the performance of individual docking, a result also corroborated by auto-dock vina. To further establish the efficacy and degradability of this approach, computational techniques were employed. In the future, it may be possible to create an in vitro antifungal agent, which could be categorized as a bioactive agent.

Exploring the Mechanism of Huoxiang Zhengqi Oral Liquid Against Mosquito Bite Dermatitis Through Network Pharmacology and in Vitro Validation

Objective: Traditional Chinese patent medicine Huoxiang Zhengqi Oral Liquid (HXZQOL) can be used topical to treat mosquito bite dermatitis (MBD). The study aimed to explore the potential mechanism of HXZQOL in treatment of MBD based on network pharmacology and experimental validation. Methods: TCMSP, SwissTargetPrediction and PubChem database were used to predict the active compounds and targets of HXZQOL and GeneCards database was utilized to predict the potential targets of MBD. Target interaction analysis was performed using Venn database, PPI and core targets were assessed using String database, and Cytoscape. Enrichment analysis on Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed using David online tool. “HXZQOL-compound-target-pathway-MBD” networks were constructed using Cytoscape. Molecular docking was carried out with Autodock vina. The inflammation model of HaCaT cells induced by TNF-a/IFN-γ was established .to validate the mechanism of HXZQOL against MBD, with the levels of inflammatory factors and protein related to IL-7 signaling pathway assessed using Elisa and Western Blot. Results: HXZQOL contained 154 active compounds and shared 88 common targets with MBD. Quercetin, apigenin, ursolic acid and luteolin were identified as potential candidate compounds, while JUN, IL-6, TNF and VEGFA were suggested as main potential targets. HXZQOL was found to act on MBD through multiple pathways including IL-17, AGE-RAGE and TNF signaling pathways. The candidate compounds demonstrated effectively binding to JUN and IL-6 targets, with binding energies below −5 kcal/mol. Western blot experiments confirmed that these compounds could down-regulate the expression of JUN protein in IL-17 signaling pathway, and significantly reduce levels of inflammatory factors TNF-α, IL-6 and NO in HaCaT cells. Conclusion: HXZQOL mainly exerts its anti MAD effect by reducing inflammation. The relevant results have laid the foundation for improving the local anti MBD effect of HXZQOL and the secondary development of HXZQOL formulations.

Antiasthamatic Activity of Betulinic Acid as a Current Bioactive Compound in an Experimental Model

aims: The purpose of this study was to assess BA&amp;#039;s effectiveness in treating bronchial asthma and to use molecular docking to find BA&amp;#039;s binding energy with β-adrenoceptor. background: The natural triterpenoid molecule betulinic acid (BA) has many biological and therapeutic uses, one of which is the relief of asthma symptoms. objective: The purpose of this study was to assess BA&amp;#039;s effectiveness in treating bronchial asthma and to use molecular docking to find BA&amp;#039;s binding energy with β-adrenoceptor. method: Methods: The extraction technique involved the use of ethanol as a solvent and the herb Bacopa monnieri. Budesenoid was used as a standard drug. AutoDock vina in PyRx 0.8 was used for the molecular docking investigation. An acute toxicity examination was conducted according to OECD guideline 425. A guinea pig model of asthma called anaphylactic microshock was employed to ascertain the antiasthmatic efficacy of the medication under investigation. Antiasthmatic activity was performed by dividing the animals into four groups each containing six animals. Group 1 was the control group received only vehicle. Group 2 was the standard group received budesenoid. Group 3 was the test group received B. monnieri extract. Group 4 was the test group received betulinic acid (BA). result: Results: In terms of binding affinity, BA has a value of -7.45 kcal/mol. In line with earlier findings, molecular docking showed that BA bound to the hydrophobic cavity of LOX-5, and the formation of hydrogen bonds altered the micro-environment and structure of LOX-5. This resulted in a reduction in enzyme activity. The mean pre-convulsion time for Drug-1 was 506.66 in comparison to the control group as observed in guinea pig model of asthma. conclusion: Conclusion: It may be a good analytical approach to test BA or BA derivatives with a stronger antiasthmatic profile with the help of computed properties. BA was found effective in reducing anaphylaxis in animal model, thus, it may be useful against asthma. other: Conclusion: It may be a good analytical approach to test BA or BA derivatives with a stronger antiasthmatic profile with the help of computed properties. BA was found effective in reducing anaphylaxis in animal model, thus, it may be useful against asthma.