AutoDock Tools Research Articles

Ligand-based in silico Approach for Identifying Potent Antidotes Against Botulinum Neurotoxin Serotype A, B, E, and F

Introduction: Botulinum neurotoxins are the most poisonous substances reported and listed in category ‘A’ of biowarfare agents. As serotype identification is a time-consuming process and there is no antidote commercially available, the development of inhibitors against serotypes causing human botulism would be beneficial. In the present study, a ligand-based in silico method was applied to identify the “hits” that could have the potential to act as counter-measures against human-intoxicating BoNTs. Methods: For this purpose, a computational approach using Molegro Virtual Docker and Auto-Dock tools was performed, where around thirty-five derivatives were designed and docked into the catalytic domain of BoNT/A, B, E, and F. The designed compounds were also studied for their ADME properties using an online web tool. Results: Analysis of the molecular docking data of the complex by Molegro Virtual Docker revealed a high binding affinity between the target and designed ligands, with the MolDock score between -139.85 and -88.24 kcal/mol, whereas the AutoDock score ranged between -11.65 and -5.30 kcal/mol. Three SMNPIs, A11, A18, and A20, exhibited better binding affini-ties with the target proteins BoNT/A, /B, E, and /F and could be potential pan-active inhibitors. The ADME/T study showed that the designed ligands were less toxic and possessed drug-re-semblance properties by considering the Lipinski, Ghose, Veber, and Egan rules, with a bioa-vailability score of 0.56. Conclusion: Our study provides insight into ‘hits’, which can lead to further progress in exper-imental studies and the development of new antidotes for botulism

Synthesis, characterization, quantum chemical modelling, molecular docking, in silico and in vitro assessment of 3-(2-bromo-5-fluorophenyl))-1-(thiophen-2-yl)prop-2-en-1-one

α,β-unsaturated carbonyl compounds have extensive applications in various fields, such as organic, inorganic, analytical, and biological. In the modern era, they offer excellent pharmacological application prospects and find widespread use in the pharmaceutical industry. The current study revealed the synthesis and characterization of a novel 3-(2-bromo-5-fluorophenyl)-1-(thiophen-2-yl) prop-2-en-1-one (CY3). In vitro their antimicrobial (Pseudomonas aeruginosa, Klebsiella pneumonia, Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii), antifungal ( Candida parapsilosis, Candida tropicalis, and Candida albicans), cytotoxicity (VERO and Hep-G2 cells), in silico, and molecular docking analysis were also performed. The in-silico analysis evaluated the drug-likeness properties of the compound CY3 using various filtering rules, including Lipinski’s, Ghose filter, Veber, Egan, Muegge, and Medicinal Chemistry alerts such as Pan Assay Interference Structures (PAINS), Brenk, and Lead-likeness. Then, molecular docking studies performed using the AutoDock (AD4), Vina, and iGEMDOCK tools to determine the mechanism by which the CY3 compound interact with the bacterial strains. Here, five different receptors were selected, such as DNA gyrase, glucose 6-phosphate synthase (GlmS), dihydrofolate reductase (DHFR), dehydrosqualene synthase (DHSS), and undecaprenyl pyrophosphate synthase (UDPPS), for molecular docking analysis. The CY3 compound showed a good binding affinity with the two target proteins, DHFR and DHSS, respectively, with maximum binding energies of about − 7.07 and − 7.05 kcal/mol. The synthesized CY3 compound exhibited moderate antibacterial activity with a MIC value > 100 µg/mL against all five bacterial strains and moderate antifungal activity with a MIC value > 50 µg/mL against all three fungal strains. Drug-likeness analyses also support their favourable bioavailability.

Kaempferol alleviates rheumatoid arthritis through pyroptosis based on bioinformatics analysis and experimental validation

Kaempferol has an anti-inflammatory effect on rheumatoid arthritis (RA), but the mechanism by which inflammatory reactions are relieved via pyroptosis is still unclear. In the present study, The bioinformatics technology was used to analyze the relationship between pyroptosis the hub genes and the downstream cytokines in RA from three the Gene Expression Omnibus (GSE12021, GSE1919 and GSE29746). Molecular docking analysis of kaempferol and caspase1 (CASP1) was executed with Autodock tools. RA fibroblast-like synoviocytes (RA-FLS) was used to explore the anti-inflammatory effects of kaempferol on RA via pyroptosis. Thirty-seven differentially expressed genes (DEGs) were identified from the three datasets, and the enrichment analysis was focused mainly on the chemokine signaling pathway. The difference in immune cell infiltration was focused on CD4 T cells, CD8 T cells, M1 macrophages, and M2 macrophages. The expression of CASP1 and caspase3 (CASP3) was higher in the RA group. CASP1 and CASP3 were positively correlated with cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Moreover, molecular docking revealed that kaempferol strongly interacts with CASP1. Kaempferol inhibited the proliferation and migration of RA-FLS in vitro. The expression of CASP1, CASP3, caspase5 (CASP4), caspase5 (CASP5), gasdermin D (GSDMD), N-terminal domain of gasdermin D (GSDMDNT), IL-1β, and cytokines interleukin-18 (IL-18) were significantly affected by kaempferol. Kaempferol alleviated RA-FLS membrane disruption, and it blocked CASP1 to alleviate RA via pyroptosis. The present study demonstrated that kaempferol binds to CASP1 and affects pyroptosis in RA, thereby serving as an anti-immunotherapy strategy.

Molecular Docking: Study of Chalcone Derivatives from Boesenbergia pandurata Targeting Estrogen Receptor Alpha (ER–a) for Breast Cancer

The increasing number of cancer patients and the challenge of multidrug resistance (MDR) demand more effective drugs, which can be developed by modifying compounds derived from natural resources, such as the flavonoid-rich temu kunci rhizome (Boesenbergia pandurata (Roxb.) Schlecht.). This study aims to predict the cytotoxicity and toxicity of 20 Pinostrobin derivatives and 19 Chalcone derivatives as potential anticancer candidates. Estrogen receptor alpha (ER-α), a validated cancer therapy target, was used for molecular docking in in silico tests using Molecular Graphics Laboratory (MGL) Tools (including, AutoDock Vina, AutoDock Tools 4.1, and Python 2.5.2) and PyRx Program. Toxicity was predicted using the pkCSM program and Protox online tool. The docking process involved binding the compounds to ER-α (PDB IDs 6CHZ and 3ERT), with the binding energy indicating activity; lower binding energy values suggest greater cytotoxic potential and stronger ligand-receptor interactions. The results showed that Chalcone derivatives from temu kunci exhibited lower toxicity and higher cytotoxic activity compared to Pinostrobin derivatives and the reference compound, Tamoxifen (TAM). Notably, Bis-3-chlorobenzyloxychalcone and Bis-2-chlorobenzyloxychalcone demonstrated the highest predicted cytotoxic activity. In conclusion, Chalcone derivatives are promising candidates for further development as more effective anticancer drugs, especially those that outperform Tamoxifen. These findings highlight the potential of natural compounds, particularly Chalcone derivatives, in combating cancer while addressing the growing challenge of MDR in clinical treatments.

Exploring the anti-inflammatory and anti-apoptotic properties of phloroglucinol on pancreatic cells in diabetic models: In silico and in vivo study

Pancreatic cell damage in diabetes mellitus is closely linked to inflammation and apoptosis. This study aimed to investigate the protective effects of phloroglucinol on pancreatic cells in a streptozotocin-induced diabetic model by assessing its anti-inflammatory and anti-apoptotic mechanisms. Phloroglucinol ligand and the structures of Bax, Bcl-2, and caspase-3 proteins were sourced from the PubChem database. Molecular docking was performed using Autodock Tools and docking results were analyzed with PyRx software. In addition, during the in vivo study, the BALB/c mice were grouped into four categories: healthy control, untreated streptozotocin-induced diabetic, and streptozotocin-induced diabetic treated with two doses of oral phloroglucinol at 100 mg/kg and 200 mg/kg body weight. After 28 days, pancreatic tissues were collected for flow cytometric analysis of NF-κB, IL-6, TNF-α, and apoptotic markers (Bax, Bcl-2, and caspase-3). The docking simulations revealed specific binding interactions: phloroglucinol interacted with Bcl-2 via amino acid residues of ALA90 and TYR139, with Bax via ALA42, LEU45, ALA46, LEU47, PRO130, and ILE133, and with caspase-3 through ARG64, SER120, GLN161, CYS163, and ARG207. The binding affinities for Bax, Bcl-2, and caspase-3 were -5.0, -4.7, and -4.9 kcal/mol, respectively. In vivo, results showed that streptozotocin significantly elevated inflammatory cytokines NF-κB, TNF-α, and IL-6, along with apoptotic markers in pancreatic cells (p<0.05) compared to healthy controls. Phloroglucinol administration at 200 mg/kg significantly reduced TNF-α, NF-κB and IL-6 levels. Phloroglucinol also prevented streptozotocin-induced pancreatic cell damage through anti-apoptotic effects by downregulating Bax and caspase-3 and upregulating Bcl-2. These findings suggest that phloroglucinol may offer protective benefits in diabetic conditions by modulating apoptotic and inflammatory pathways.

Mechanism of traditional drug treatment of cancer-related ascites: through the regulation of IL-6/JAK-STAT3 pathway.

Our clinical observation found that JiJiaoLiHuang Pill (JJLH), a classic traditional Chinese medicine (TCM) formulation, can significantly reduce the abdominal circumference of patients with malignant ascites, increase urine output, and improve the quality of life of patients, with preliminary efficacy. But, the exact mechanism is not yet clear. Based on the above observations, the potential mechanism of action of the treatment was preliminarily explored. We identified active ingredients by constructing a "Chinese medicine ingredient-key target-target" network, and verified them by molecular docking using AutoDock tools and PyMOL. Finally, we conducted preliminary verification of the validated pathways and targets using a mouse model of liver cancer ascites. Network pharmacology analysis obtained the top five active ingredients were quercetin, EUPATIN, kaempferol, Obtucarbamate B, and isorhamnetin and the top five key genes were SRC, HSP90AA1, MAPK1, STAT3, and PIK3CA. Molecular docking showed that all 5 active compounds were closely bound to key target genes (binding energy <-6). The animal experiment results showed that JJLH can significantly reduce abdominal circumference, increase urine output, and exhibit dose-dependent inhibition of the AQP-3/JAK-STAT-3 signaling pathway and the expression of related inflammatory factors. The JJLH potentially inhibits the recurrence of liver cancer malignant ascites through the AQP-3/JAK-STAT-3 pathway and affects the prognosis of MA patients.

In silico and in vivo evaluations of fisetin and fisetin-loaded nanosuspension on monoamine oxidase inhibition in Aβ(25–35) induced dementia in mice model

BackgroundAmyloid beta (Aβ) plaques on the extracellular matrix and intracellular neurofibrillary tangles comprise the key indicative pathology of Alzheimer's disease (AD). Fisetin, an antioxidant bioactive compound having pharmacotherapeutic effects is applied by traditional Chinese medicine (TCM) such as Toxicodendron vernicifum (Chinese lacquer tree), Cotinus coggygria Scop, Gan Shuang granulates and formula of Acacia catechu-Scutellariae Radix. Nevertheless, fisetin has constraints such as low oral bioavailability, insignificant aqueous solubility and high hepatic metabolisms. ObjectiveThis investigation aimed to envisage the effects of fisetin and its optimised nanoformulation on Aβ(25–35) desirous neurotoxicity in mice through deciphering inhibitory actions against monoamine oxidase A and B (MAO-A and B) enzymes following molecular docking. MethodsMolecular docking with MAO-A and B enzymes were accomplished by AMDock's integrated AutoDock Tools (ADT) scripts. For in vivo studies, fisetin nanosuspension was prepared by nanoprecipitation method and evaluated for standard characterization. 10 and 20 mg/kg of fisetin and 10 mg/kg of fisetin nanosuspension were given once daily to mice for 21 days. On the 15th day, the mice were challenged with Aβ(25–35) by intracerebroventricular injection (ICV) and behavioural tests (open field and elevated plus maze) were performed on the 20th day. Biochemical and histology were examined in brain tissues. ResultsFisetin docked to the catalytic positions of MAO-A and B, unveiling good binding scores and molecular interactions with amino acid residues for inhibition activities. Fisetin nanosuspension has average particle size (225.4 ± 2.95 nm) with low polydispersity index (0.19) and standard zeta potential (-19.13 ± 1.17 mV). Findings showed that fisetin increased locomotor activity and reduced anxiety-like behaviour. Fisetin and its nanosuspension significantly reduced the concentration of MAO-A (P < 0.01) and MAO-B enzymes suggesting a potential neuroprotection effect in Aβ peptide-induced amnesia in mice. ConclusionFisetin with optimized bioavailability, effectively exhibits neuroprotection through molecular interactions of MAO enzymes. Further investigations affidavits the neuroprotection through bidirectional pathways related to biogenic amines and their deamination on Aβ stress conditions.

Design, Synthesis, and Antitumor Potential of New Thiazole--contained 5-Fluoro-2-Oxindole Derivatives as Sunitinib Analogues.

Indole is considered the most promising scaffold for anticancer drug design due to its high bioavailability, unique chemical properties, and broad spectrum of pharmacological action. Twelve novel thiazole-containing the 5-fluoro-1,3-dihydro-2H-indol-2-one derivatives as sunitinib analogs were designed and synthesized, and their anticancer activity was evaluated against the NCI-60 cancer cell lines. The thiazole-contained 5-fluoro-1,3-dihydro-2H-indol-2-one derivatives were synthesized using Knoevenagel condensation of 1,3-thiazole-5-carboxylic acid 1. Their anticancer activities were evaluated by NCI-60 one-dose screen assay. The molecular docking studies were performed using AutoDock tools and the AutoDock Vina programs. The ADMETlab 2.0 web server predicted the physicochemical properties of compounds. Among the synthesized new 5-fluoro-2-oxindole derivatives, compound 3g demonstrated high antitumor activity (GI>70%) against eight types of cancer: leukemia, breast cancer, ovarian cancer, lung cancer, melanoma, CNS cancer, renal cancer, and colon cancer. The most activity was observed against breast cancer (T-47D, GI=96.17%), lung cancer (HOP-92, GI=95.95%), ovarian cancer (NCI/ADR-RES, GI=95.13%), and CNS cancer (SNB-75, GI=89.91%). The molecular docking results of compound 3g demonstrated the possibility of inhibiting VEGF2 receptors as his potential anticancer mechanism. The physicochemical properties predicted for compounds 3f and 3g showed positive results. Compound 3g demonstrated high in vitro NCI-60 anticancer activity against nine cancer types and showed cell growth inhibition against leukemia, CNS, and breast cancer at 6 - 31% higher than Sunitinib, and may represent the basis for further modification of the thiazole-containing analogs of the anticancer drug Sunitinib.

In silico exploration of phytocompounds from AYUSH-64 medicinal plants against SARS CoV-2 RNA-dependent RNA polymerase

BackgroundThe AYUSH 64 formulation helps to treat mild to moderate cases of COVID-19. Although several drugs have been proposed to combat COVID-19, no medication is available for SARS-CoV-2 infection. The RNA-dependent RNA polymerase (RdRp) is the pivotal enzyme of SARS-CoV-2 replication, so it could be considered a better drug target for experimental studies. ObjectiveThe AYUSH-64 formulation plants exhibited multiple therapeutic properties; thus, the present study aims to screen the phytocompounds of these plants against SARS CoV2 RdRp to identify specific compounds that could potentially affect COVID-19 infection. Materials and methodsPatchDock and AutoDock tools were used for docking experiments. MD simulations and Density Functional Theory (DFT) calculations of protein-ligand Picroside-I and Remdesivir complexes were carried out in GROMACS v2019.4 and Gaussian 09 software, respectively. ResultsAmong the tested, five phytocompounds (Picroside I, Oleanolic acid, Arvenin I, II, and III) from AYUSH-64 medicinal plants showed possible binding with RdRp catalytic residues (Ser759, Asp760, and Asp761). Of these, Picroside I exhibited hydrogen bond interactions with NTP entry channel residues (Arg553 and Arg555). The MM-PBSA free energy, RMSD, Rg, PCA, and RMSF analysis suggested that the Picroside I complex showed stable binding interactions with RdRp in the 50 ns simulation. In addition to this, Picroside I revealed its robust and attractive nature toward the target protein, as confirmed by DFT. ConclusionThe results of this study have proposed that Picroside I from AYUSH 64 medicinal plant compounds was the selective binder of catalytic and NTP entry channel residues of SARS-CoV2 RdRp thereby; it may considered as a potential inhibitor of SARS-CoV2 RdRp.

Synergistic Action of Rutin-Coated Zinc Oxide Nanoparticles: Targeting Biofilm Formation Receptors of Dental Pathogens and Modulating Apoptosis Genes for Enhanced Oral Anticancer Activity.

Oral diseases are often associated with bacterial and fungal pathogens such as Staphylococcus aureus, Streptococcus mutans, Enterococcus faecalis, and Candida albicans. This research explored a novel approach to addressing these pathogens by synthesizing zinc oxide nanoparticles (ZnO NPs) coated with rutin (RT), a plant-derived compound. The synthesized ZnO-RT NPs were comprehensively characterized using UV-Vis spectrophotometer, SEM, and EDAX techniques to confirm their structural composition. The antioxidant potential was assessed through free radical scavenging assays. Additionally, the antimicrobial activity of ZnO-RT NPs was evaluated using a zone of inhibition assay against oral pathogens. Molecular docking studies with the Autodock tool were performed to elucidate the interactions between RT and the receptors of oral pathogens. The findings demonstrated that ZnO-RT NPs exhibited robust free radical scavenging activity. Furthermore, they showed significant antimicrobial activity with a minimal inhibitory concentration of 40 μg/mL against oral pathogens. ZnO-RT NPs also displayed dose-dependent anticancer effects on human oral cancer cells at concentrations of 10, 20, 40, and 80 μg/mL. Mechanistic insights into the anticancer activity on KB cells revealed the upregulation of apoptotic genes. This study underscores the promising potential of ZnO-RT NPs for dental applications due to their strong antioxidant, anticancer, and antimicrobial properties. These nanoparticles offer a hopeful prospect for addressing oral pathogen challenges and enhancing overall oral health.

A Network Pharmacology Study on Mechanism of Total Flavonoids of Hippophae Rhamnoides in Treating Allergic Dermatitis via Regulation of IL-17 Signaling Pathways

Objective: This study aims to investigate the active ingredients and potential mechanisms of Total Flavonoids of Hippophae (TFH) in the treatment of Allergic Dermatitis (AD) using network pharmacology and molecular docking. Methods: The effective components and targets of TFH were identified using the TCMSP, Pub- Chem, and Pharmmapper databases. AD-related targets were screened through GeneCards, OMIM, and TTD databases, leading to the identification of TFH anti-AD related targets. The STRING database was utilized to obtain protein interaction relationships, and Cytoscape 3.9.0 software was employed to construct the protein-protein interaction network. GO and KEGG enrichment analyses were conducted to elucidate the biological processes and pathways involved. Molecular docking between key components and key targets was verified using AutoDock Tools 1.5.6 software. Results: The key components identified for anti-AD activity were Quercetin, Kaempferol, Cianidanol, and Epicatechin, while the key targets included MAPK8, MAPK10, MAPK14, AKT1, SRC, and EGFR. GO analysis indicated that TFH's anti-AD effects are primarily associated with hormone regulation, cellular processes, response to stimuli, organelles, and cytoplasm. KEGG enrichment analysis suggested that the key pathways involved are pathways in cancer, lipid and atherosclerosis, and the IL-17 signaling pathway, with a significant emphasis on the IL-17 signaling pathway. Molecular docking results demonstrated that the key active ingredients exhibited strong binding activity with all the key targets, with the highest binding affinities observed between kaempferol and MAPK14, epicatechin and MAPK14, and quercetin and AKT1. Conclusion: TFH exerts therapeutic effects on atopic dermatitis through multi-component, multitarget, and multi-pathway mechanisms involving inflammatory response, immune regulation, and apoptosis. This study provides valuable insights for the further development of drugs specifically targeting AD.

A Preliminary Antidepressant Assessment of a Novel Piperoyl Amide (Y3) Isolated and Elucidated from Piper nigrum Drupes Extract, Justifying Interaction Over MAO-A enzyme: An in vivo, in vitro and Molecular Docking Approach

This research aims to confirm the preliminary antidepressant activity of a newly discovered piperoyl amide (Y3) obtained from the extract of Piper nigrum (P. nigrum) drupes, through the inhibition of MAO-A enzyme. Column chromatography was employed for isolation and purification of Novel piperoyl-alkyl amide (Y3) which was eluted in a solvent mixture of Chloroform-Methanol (97:3). Structure elucidation was performed by implying spectroscopic techniques. Invitro in-comparison MAO activity assessment was performed between Y3 and piperine further confirmed by Molecular docking via Auto Dock Tools 1.5.6, Vina, and PyMOL. Invivo antidepressant activity was evaluated by the Despair Test in albino mice. Novel piperoyl-alkyl amide (Y3) was isolated and purified by column chromatography and elucidated spectroscopically. The antidepressant activity of Y3 at 10 and 20 mg/kg doses shown a significant decrease in immobility-time (IT) in contrast to stressed-control group at 107.0±7.6 sec (P&lt;0.05) and 96.0±7.6 sec (P&lt;0.01), respectively. Y3 shown a decent MAO-A inhibitory activity but lower than piperine showing IC50=20.24 µM, Vmax=1.375±0.3 nM/min/mg, Km=1.379×10-16 µM with a stronger interaction and better affinity (-12.6 kcal/mol) towards the active-site of MAO-A. Y3 was isolated and elucidated as (12E,14E)-15-(benzo[d] [1,3] dioxol-5-yl)-N-ethylpentadeca-12,14-dienamide. It proved a good antidepressant at 10 and 20 mg/kg doses. Molecular docking over MAO-A and QSAR studies depicted a better affinity score of Y3 than Piperine. Keywords: Piperoyl amide, Structure elucidation, antidepressant activity, molecular modeling, Piperine

Unveiling the Potential Bioactive Peptides Derived From Goat Casein Hydrolysates Based on In Silico Analyses

ABSTRACTBioactive peptides (BAPs) have attracted considerable interest in scientific research due to their heterogeneity in sequence and structure, which underpins various biological functionalities. In this context, goat casein, an abundant by‐product of the dairy industry, emerges as a valuable source of BAPs. The present study undertook a meticulous evaluation of the bioactive potentials of goat casein‐derived peptides through an integrated approach combining computational simulations, high‐throughput screening, and molecular docking techniques. The initial phase involved the enzymatic digestion of goat milk casein using trypsin, followed by the identification of peptides via liquid chromatography–tandem mass spectrometry (LC–MS/MS), uncovering a total of 597 peptides. Subsequent prioritization using the PeptideRanker algorithm identified 70 peptides exhibiting potential bioactivity, as denoted by scores above 0.8. Advanced screening employing the BIOPEP database and the AutoDock and CAMPR4 tools facilitated the elucidation of 16 antioxidant, 59 hypotensive, 63 hypoglycemic, 70 hypolipidemic, and 25 antimicrobial peptides. Molecular docking studies further elucidated the spontaneous nature of the interactions between the peptides and their respective receptors, predominantly mediated by hydrogen bonding and hydrophobic interactions. Four peptides specifying all activities simultaneously were synthesized, and their activities were verified by in vitro experiments. These results not only highlight an effective strategy for the high‐throughput screening of goat casein‐derived peptides but also underscore the potential of utilizing casein as a viable source of functional food ingredients. This study thereby contributes significantly to the expanding field of functional food research, suggesting a sustainable approach to explore the potential of dairy by‐products.

Molecular Docking to Predict a Novel Bioactive Compound as an Inhibitor of Beta Catenin in Oral Squamous Cell Carcinoma

Background: Efforts aimed at enhancing patient survival have focused on early detection and diagnosis, followed by prompt treatment of potentially malignant disorders, aiming to halt their advancement into oral cancer. Recent research has shed light on the pivotal role of the Wnt/B-catenin signaling pathway in the pathogenesis of potentially malignant oral conditions. This pathway undergoes a progressive activation process across various degrees of epithelial dysplasia, including mild, moderate, and severe dysplasia. Beta-catenin (B-catenin) triggers the activation of genes associated with crucial cellular processes, which include cell growth, viability, differentiation, and migration. Aims: In the present study, we aimed to design a novel drug with 3 bioactive compounds through insilico analysis, assess its efficacy against B-catenin, and develop a new pharmacophore with an emphasis on B-catenin inhibition. Materials and Methods: Based on prior literature, three molecules possessing potent beta-cateninblocking properties were selected, namely rosmarinic acid, zosterin, and stigmasterol. To evaluate their binding affinities, molecular docking studies were conducted using the Lamarckian Genetic Algorithm implemented in AutoDock Tools 1.5.7. Initially, AutoGrid was employed to construct a grid box for docking purposes. The estimated binding poses of each compound were subjected to clustering analysis. The interactions between the compounds and beta-catenin were visualized and explored using PyMOL software. Results: Stigmasterol displayed the most substantial binding energy with a value of -3.86 kcal/mol, followed by rosmarinic acid and zosterin. Conclusion: Bioactive components can be used for beta-catenin pathway blocking. Future research should be carried out to assess these substances in more clinically relevant cancer models.

Molecular interactions of plant-derived inhibitors from Euphorbia hirta against binding sites of HPV E6 and E7 oncoproteins - An in-silico analysis

Although no cure for Human Papilloma virus (HPV) exists at the moment, effective vaccines are present that can prevent the most harmful strains of the virus from infecting people. While potential cures like therapeutic vaccines, immunotherapy, and gene therapy are still in the early stages of development and may take years to become widely available, we focussed on using traditional Siddha-based medicines (phytochemicals of Euphorbia hirta L.) as a prospect through in-silico docking studies. Twelve phytochemicals from Euphorbia hirta L. were selected to investigate the antiviral properties against HPV. These ligand structures were obtained from PubChem database, prepared for docking with two major HPV targets i.e., E6 and E7 oncoproteins obtained from PDB, using AutoDock tools. The analysis revealed the potential of lobeline and euphol ligands effectively binding to the active sites of E6 and E7 proteins respectively. Using the ADMET lab 2.0 server, the ligands were evaluated for their commercial drug potential by considering their absorption, distribution, metabolism, excretion, and toxicity properties.

Intercalating compounds alongside DNA helicase Q1 Plasmodium falciparum 3D7: Assessments of the Pharmacokinetic Properties Prediction of ADME.

Quantum chemical & molecular docking practices to deliver new perceptions into how etoposide, novobiocin, nogalamycin and netropsin interact with the biological targets PF3D7_0918600 (Plasmodium falciparum 3D7). Further the pharmacokinetics of a drug candidate which influenced by a variety of factors, including P- glycoprotein (Pgp) transport, PBB (Plasma protein binding), & BBB (Blood-brain barrier) permeation help to forecast the pharmacological characteristics of acetyl-CoA reductase inhibitors (ADMEs) and their metabolites. At this point, we have elevated four compounds such as etoposide, novobiocin, nogalamycin & netropsin. We have also studied molecular docking against the target protein of the Plasmodium falciparum (PF3D7_0918600) through exhausting the AutoDock Vina platform and AutoDock-Tools (ADT) and pharmacokinetic properties were carried out using the ADMET 2.0. The relative results of molecular docking recommended a greater binding affinity of novobiocin with the selected receptors among other compounds. In-silico ADME screening is a computational approach utilised to forecast the pharmacological characteristics of acetyl- CoA reductase inhibitors (ADMEs) and their metabolites. The ADMEs are based on the adsorption-desorption kinetics and pharmacopoeia. Adsorption and distribution analysis are used to assess the potential of the drug candidate. In vitro ADME is exploited to expect the effect of Pgp transport on the drug candidates. ADME has been used to predict CYP1A2 inhibitors and to predict PPB and BBB penetration. This paper summarizes the current knowledge on molecular docking, ADME and identifies potential drug candidates for ADME in vitro and in vivo.

Competing Endogenous TMPO-AS1-let-7c-5p- LDHA RNA Network Predicts the Prognosis of Lung Adenocarcinoma Patients.

Lactate dehydrogenase is dysregulated in several cancer types. However, the mechanism of its dysregulation in lung cancer is not fully understood. We utilized web-based computational databases to conduct gene expression analysis on LDHA, identified its regulator, and explored their role in the prognosis of lung cancer. We used various web-based computational tools, including the UALCAN, TIMER2.0, ENCORI, TCGA Portal, OncoDB, and GEPIA2 datasets for lung cancer analysis in this study. We also performed survival, biological processes, and metastasis analysis using various computational tools. We also carried out co-expression functional enrichment analysis using the Enrichr and TIMER databases, multivariate analysis of survival and pathological stage, and transcriptional regulation analysis using the ENCORI and OncoDB datasets. Furthermore, LDHA inhibitor binding of withanolides was analyzed using Auto Dock Tools 1.5.6, LigPlot+, and Pymol. The study found that the higher levels of LDHA gene expression were associated with poor prognosis and overall survival in lung cancer patients. We identified 11 key genes co-expressed with LDHA; out of them, two genes, MKI67 and PGK1, showed a strong positive correlation with LDHA and associated poor survival outcomes in LUAD patients. Furthermore, we also identified hsa-let-7c-5p and TMPO-AS1 as potential regulators of LDHA in LUAD. It might be possible that the TMPO-AS1- hsa-let-7c-5p-LDHA ceRNA network could serve as a potential regulator of aerobic glycolysis in LUAD and can serve as prognostic biomarkers. Further, Withanolides can inhibit the activity of LDHA and can be tested as an adjuvant treatment. We conclude that LDHA is overexpressed in LUAD, and the patients with high expression of LDHA exhibit poor prognosis. Further, the TMPO-AS1-hsa-let-7c-5p-LDHA ceRNA network can regulate aerobic glycolysis, thereby facilitating tumor growth in lung cancer.

Potential involvement of connective tissue growth factor in chondrocytes apoptosis of Kashin-Beck disease

BackgroundKashin-Beck disease (KBD) is an endemic osteoarthropathy characterized by excessive chondrocytes apoptosis. T-2 toxin exposure has been proved to be its etiology. Connective tissue growth factor (CTGF) exerts a profound influence on cartilage growth and metabolism. We investigated the potential role of CTGF in KBD development and examined CTGF alterations under T-2 toxin stimulation. MethodsThe levels of CTGF and chondrocyte apoptosis-related markers in cartilage and primary chondrocytes from KBD and control groups were measured using qRT-PCR, Western blotting, immunohistochemistry, and immunofluorescence. We analyzed expression changes of these genes in response to T-2 toxin. Apoptosis rates of chondrocytes induced by T-2 toxin were measured by flow cytometry and TUNEL assay. The active pharmaceutical ingredient targeting CTGF was screened through Comparative Toxicogenomics Database, and molecular docking was performed using AutoDock Tools. ResultsThe CTGF levels in KBD cartilage and chondrocytes were significantly elevated and positively associated with the levels of apoptosis-related genes. T-2 toxin exposure increased CTGF and apoptosis-related gene levels in chondrocytes, with apoptosis rates rising alongside T-2 toxin concentration. Curcumin was identified as targeting CTGF and exhibited effective binding. It could down-regulate CTGF, apoptosis-related genes, such as Cleaved caspase 3 and BAX, and also significantly reduce apoptosis rate in chondrocytes treated with T-2 toxin. ConclusionCTGF plays a crucial role in the development of KBD. Curcumin has shown potential in inhibiting CTGF levels and reducing chondrocyte apoptosis, highlighting its promise as a therapeutic agent for preventing cartilage damage in KBD. Our findings provided valuable insights into the pathogenesis of KBD and could promote the development of novel therapeutic strategies for this debilitating disease.

Exploring the Mechanisms of Self-made Kuiyu Pingchang Recipe for the Treatment of Ulcerative Colitis and Irritable Bowel Syndrome using a Network Pharmacology-based Approach and Molecular Docking.

Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are common intestinal diseases. According to the clinical experience and curative effect, the authors formulated Kuiyu Pingchang Decoction (KYPCD) comprised of Paeoniae radix alba, Aurantii Fructus, Herba euphorbiae humifusae, Lasiosphaera seu Calvatia, Angelicae sinensis radix, Panax ginseng C.A. Mey., Platycodon grandiforus and Allium azureum Ledeb. The aim of the present study was to explore the mechanisms of KYPCD in the treatment of UC and IBS following the Traditional Chinese Medicine (TCM) theory of "Treating different diseases with the same treatment". The chemical ingredients and targets of KYPCD were obtained using the Traditional Chinese Medicine Systems Pharmacology database and analysis platform (TCMSP). The targets of UC and IBS were extracted using the DisGeNET, GeneCards, DrugBANK, OMIM and TTD databases. The "TCM-component-target" network and the "TCM-shared target-disease" network were imaged using Cytoscape software. The protein-protein interaction (PPI) network was built using the STRING database. The DAVID platform was used to analyze the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Using Autodock Tools software, the main active components of KYPCD were molecularly docked with their targets and visualized using PyMOL. A total of 46 active ingredients of KYPCD corresponding to 243 potential targets, 1,565 targets of UC and 1,062 targets of IBS, and 70 targets among active ingredients and two diseases were screened. Core targets in the PPI network included IL6, TNF, AKT1, IL1B, TP53, EGFR and VEGFA. GO and KEGG enrichment analysis demonstrated 563 biological processes, 48 cellular components, 82 molecular functions and 144 signaling pathways. KEGG enrichment results revealed that the regulated pathways were mainly related to the PI3K-AKT, MAPK, HIF-1 and IL-17 pathways. The results of molecular docking analysis indicated that the core active ingredients of KYPCD had optimal binding activity to their corresponding targets. KYPCD may use IL6, TNF, AKT1, IL1B, TP53, EGFR and VEGFA as the key targets to achieve the treatment of UC and IBS through the PI3K-AKT, MAPK, HIF-1 and IL-17 pathways.

Anticancer Potential of Quercetin on Oral Squamous Cell Carcinoma: A Scoping Review and Molecular Docking.

Oral squamous cell carcinoma (OSCC) is a type of cancer that has a low survival rate and high recurrence and metastasis rates. To date, there is still no effective treatment for OSCC. Various types of cancer, including OSCC, have reported quercetin to act as an anticancer agent, but there is no clear research data on how it may affect OSCC. To determine the anticancer potential of quercetin in OSCC, we conducted a scoping review, and to determine the interaction of quercetin with one of the proteins that plays a role in carcinogenesis, namely, BCL-2, we conducted molecular docking. The scoping review process was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. The scoping review was searched by collecting articles related to the research topic in Google Scholar, PubMed, ScienceDirect, Cochrane, and EBSCOhost databases. All of the literature records found during the search were imported into the Mendeley software to remove duplication. Nine studies were generated after the titles and abstracts were reviewed according to the inclusion and exclusion criteria. After the full-text screening, no studies were excluded, leaving nine publications determined to be eligible for inclusion in the scoping review. Quercetin showed effects on inhibiting cancer invasion, migration, proliferation, and many protein expressions, as well as increasing cell apoptosis. Molecular docking was done for quercetin and BCl-2 protein. Doxorubicin was utilized as a comparison ligand. The in silico study was utilized using AutoDock Vina, AutoDock Tools 1.5.6, Biovia Discovery Studio 2021, and PyMol. Molecular docking indicated quercetin has a strong binding affinity with BCl-2 protein (ΔG -7.2 kcal/mol). Both scoping review and molecular docking revealed that quercetin is a promising candidate for anticancer agent.