Biological effects of Bougainvillea glabra, Delonix regia, Lantana camara, and Platycladus orientalis extracts and their possible metabolomics therapeutics against the West Nile virus vector, Culex pipiens (Diptera: Culicidae).

Plants are a treasure trove of biological materials containing a wide range of potential phytochemicals that are target-specific, rapidly biodegradable, and environmentally friendly, with multiple medicinal effects. Unfortunately, the development of resistance to synthetic pesticides and antibiotics led to the discovery of new antibiotics, antioxidants, and biopesticides. This has also led to the creation of new medications that work very well. The current study aimed to prove that ornamental plants contain specialized active substances that are used in several biological processes. Mosquitoes, one of the deadliest animals on the planet, cause millions of fatalities each year by transmitting several human illnesses. Phytochemicals are possible biological agents for controlling pests that are harmful. The potential of leaf extracts of Bougainvillea glabra, Delonix regia, Lantana camara, and Platycladus orientalis against Culex pipiens and microbial agents was evaluated. Acetone extracts had more toxic effects against Cx. pipiens larvae (99.0-100 %, 72 h post-treatment), and the LC50 values were 142.8, 189.5, 95.4, and 71.1 ppm for B. glabra, D. regia, L. camara, and P. orientalis, respectively. Plant extracts tested in this study showed high insecticidal, antimicrobial, and antioxidant potential. GC-MS and HPLC analyses showed a higher number of terpenes, flavonoids, and phenolic compounds. The ADME analysis of element, caryophyllene oxide, caryophyllene, and copaene showed that they were similar to drugs and that they were better absorbed by the body and able to pass through the blood-brain barrier. Our results confirm the ability of ornamental plants to have promising larvicidal and antimicrobial activity and biotechnology.

Identification of small molecule glucokinase activators for the treatment of diabetes based on plants from the traditional Chinese medicine: In silico analysis.

Mutations in glucokinase (GCK) can either enhance or inhibit insulin secretion, leading to different forms of diabetes, including gestational diabetes. While many glucokinase activators (GKAs) have been explored as treatments, their long-term effectiveness has often been unsatisfactory. However, recent interest has surged with the introduction of dorzagliatin and TTP399. This study investigates the efficacy of four previously studied compounds (Swertiamarin, Apigenin, Mangiferin, and Tatanan A) in activating GCK using computational methods. Initial molecular docking revealed binding affinities ranging from -6.7 to -8.6 kcal/mol. The compounds were then evaluated for drug-likeness and pharmacokinetic properties. Re-docking studies were performed for validation. Based on their favorable binding affinities and compliance with Lipinski's rule and ADMET criteria, three compounds (Swertiamarin, Apigenin, and Tatanan A) were selected for molecular dynamics (MD) simulations. MD simulations demonstrated that Swertiamarin showed excellent stability, as indicated by analyses of RMSD, RMSF, radius of gyration (Rg), hydrogen bonding, and principal component analysis (PCA). These results suggest that Swertiamarin holds promise for further investigation in in vivo and clinical settings to evaluate its potential in enhancing GCK activity and treating diabetes. This study assessed the potential of four compounds as GCK activators using molecular docking, pharmacokinetic profiling, and MD simulations. Swertiamarin, in particular, showed significant stability and adherence to drug-likeness criteria, making it a promising candidate for further research in combating diabetes.

Exploring TEAD2 as a drug target for therapeutic intervention of cancer: A multi-computational case study.

Transcriptional enhanced associate domain (TEAD) is a family of transcription factors that plays a significant role during embryonic developmental processes, and its dysregulation is responsible for tumour progression. TEAD is considered as druggable targets in various diseases, namely cancer, cardiovascular diseases and neurodegenerative disorders. Previous structural studies revealed the importance of the central hydrophobic pocket of TEAD as a potential target for small-molecule inhibitors and demonstrated flufenamic acid (FLU) (a COX-2 enzyme inhibitor) to bind and inhibit TEAD2 functions. However, to date, no drug candidates that bind specifically to TEAD2 with high selectivity and efficacy have been developed or proposed. Within this framework, we present here a case study where we have identified potential TEAD2 inhibitor candidates by integrating multiple computational approaches. Among the candidates, the top two ranked compounds ZINC95969481 (LG1) which is a fused pyrazole derivative and ZINC05203789 (LG2), a fluorene derivative resulted in much favourable binding energy scores than the reference ligand, FLU. The drug likeliness of the best compounds was also evaluated in silico to ensure the bioavailability of these compounds particularly LG1 as compared to FLU thus providing a strong rationale for their development as leads against TEAD. Molecular dynamics simulations results highlighted the role of key residues contributing to favourable interactions in TEAD2-LG1 complex with much favourable interaction and binding free energy values with respect to the reference compound. Altogether, this study provides a starting platform to be more exploited by future experimental research towards the development of inhibitors against TEAD, a persuasive strategy for therapeutic intervention in cancer treatment.

Discovery of VEGFR inhibitors through virtual screening and energy assessment.

Vascular endothelial growth factor receptor-2 (VEGFR-2) is crucial in promoting tumor angiogenesis and cancer metastasis. Thus, inhibition of VEGFR-2 has appeared as a good tactic for cancer treatment. To find out novel VEGFR-2 inhibitors, first, the PDB structure of VEGFR-2, 6GQO, was selected based on atomic nonlocal environment assessment (ANOLEA) and PROCHECK assessment. 6GQO was then further used for structure-based virtual screening (SBVS) of different molecular databases, including US-FDA approved drugs, US-FDA withdrawn drugs, may bridge, MDPI, and Specs databases using Glide. Based on SBVS, receptor fit, drug-like filters, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of 427877 compounds, the best 22 hits were selected. From the 22 hits, hit 5 complex with 6GQO was put through molecular mechanics/generalized born surface area (MM/GBSA) study and hERG binding. The MM/GBSA study revealed that hit 5 possesses lesser binding free energy with more inferior stability in the receptor pocket than the reference compound. The VEGFR-2 inhibition assay of hit 5 disclosed an IC50 of 165.23 nM against VEGFR-2, which can be possibly enhanced through structural modifications.

Exploring Medicinal Herbs' Therapeutic Potential and Molecular Docking Analysis for Compounds as Potential Inhibitors of Human Acetylcholinesterase in Alzheimer's Disease Treatment.

Background and Objectives: Alzheimer's disease (AD) stands as a pervasive neurodegenerative ailment of global concern, necessitating a relentless pursuit of remedies. This study aims to furnish a comprehensive exposition, delving into the intricate mechanistic actions of medicinal herbs and phytochemicals. Furthermore, we assess the potential of these compounds in inhibiting human acetylcholinesterase through molecular docking, presenting encouraging avenues for AD therapeutics. Materials and Methods: Our approach entailed a systematic exploration of phytochemicals like curcumin, gedunin, quercetin, resveratrol, nobiletin, fisetin, and berberine, targeting their capability as human acetylcholinesterase (AChE) inhibitors, leveraging the PubChem database. Diverse bioinformatics techniques were harnessed to scrutinize molecular docking, ADMET (absorption, distribution, metabolism, excretion, and toxicity), and adherence to Lipinski's rule of five. Results: Results notably underscored the substantial binding affinities of all ligands with specific amino acid residues within AChE. Remarkably, gedunin exhibited a superior binding affinity (-8.7 kcal/mol) compared to the reference standard. Conclusions: These outcomes accentuate the potential of these seven compounds as viable candidates for oral medication in AD treatment. Notably, both resveratrol and berberine demonstrated the capacity to traverse the blood-brain barrier (BBB), signaling their aptitude for central nervous system targeting. Consequently, these seven molecules are considered orally druggable, potentially surpassing the efficacy of the conventional drug, donepezil, in managing neurodegenerative disorders.

In-Silico Analysis of Phytocompounds of Olea europaea as Potential Anti-Cancer Agents to Target PKM2 Protein.

Globally, cancer is the second leading cause of mortality and morbidity. The growth and development of cancer are extremely complex. It is caused by a variety of pathways and involves various types of enzymes. Pyruvate kinase M2 (PKM2) is an isoform of pyruvate kinase, that catalyses the last steps of glycolysis to produce energy. PKM2 is relatively more expressed in tumour cells where it tends to exist in a dimer form. Various medicinal plants are available that contain a variety of micronutrients to combat against different cancers. The phytocompounds of the olive tree (Olea europaea) leaves play an important role in inhibiting the proliferation of several cancers. In this study, the phytocompounds of olive leaf extract (OLE) were studied using various in silico tools, such as pkCSM software to predict ADMET properties and PASS Online software to predict anticancer activity. However, the molecular docking study provided the binding energies and inhibition constant and confirmed the interaction between PKM2 and the ligands. The dynamic behaviour, conformational changes, and stability between PKM2 and the top three hit compounds (Verbascoside (Ver), Rutin (Rut), and Luteolin_7_O_glucoside (Lut)) are studied by MD simulations.

Cytotoxic Activity against A549 Human Lung Cancer Cells and ADMET Analysis of New Pyrazole Derivatives.

Two new pyrazole derivatives, namely compound 1 and compound 2, have been synthesized, and their biological activity has been evaluated. Monocrystals of the obtained compounds were thoroughly investigated using single-crystal X-ray diffraction analysis, FTIR spectroscopy, and NMR spectroscopy. The results gathered from all three techniques are in good agreement, provide complete information about the structures of 1 and 2, and confirm their high purity. Thermal properties were studied using thermogravimetric analysis; both 1 and 2 are stable at room temperature. In order to better characterize 1 and 2, some physicochemical and biological properties have been evaluated using ADMET analysis. The cytotoxic activity of both compounds was determined using the MTT assay on the A549 cell line in comparison with etoposide. It was determined that compound 2 was effective in the inhibition of human lung adenocarcinoma cell growth and may be a promising compound for the treatment of lung cancer.

Identification of Spiro-Fused [3-azabicyclo[3.1.0]hexane]oxindoles as Potential Antitumor Agents: Initial In Vitro Evaluation of Anti-Proliferative Effect and Actin Cytoskeleton Transformation in 3T3 and 3T3-SV40 Fibroblast.

Novel heterocyclic compounds containing 3-spiro[3-azabicyclo[3.1.0]hexane]oxindole framework (4a, 4b and 4c) have been studied as potential antitumor agents. The in silico ADMET (adsorption, distribution, metabolism, excretion and toxicity) analysis was performed on 4a-c compounds with promising antiproliferative activity, previously synthetized and screened against human erythroleukemic cell line K562 tumor cell line. Cytotoxicity of 4a-c against murine fibroblast 3T3 and SV-40 transformed murine fibroblast 3T3-SV40 cell lines were evaluated. The 4a and 4c compounds were cytotoxic against 3T3-SV40 cells in comparison with those of 3T3. In agreement with the DNA cytometry studies, the tested compounds have achieved significant cell-cycle perturbation with higher accumulation of cells in G0/G1 phase. Using confocal microscopy, we found that with 4a and 4c treatment of 3T3 cells, actin filaments disappeared, and granular actin was distributed diffusely in the cytoplasm in 82-97% of cells. The number of 3T3-SV40 cells with stress fibers increased to 7-30% against 2% in control. We discovered that transformed 3T3-SV40 cells after treatment with compounds 4a and 4c significantly reduced the number of cells with filopodium-like membrane protrusions (from 86 % in control cells to 6-18% after treatment), which indirectly suggests a decrease in cell motility. We can conclude that the studied compounds 4a and 4c have a cytostatic effect, which can lead to a decrease in the number of filopodium-like membrane protrusions.

Virtual Screening of Natural Compounds as Potential PI3K-AKT1 Signaling Pathway Inhibitors and Experimental Validation.

A computational screening for natural compounds suitable to bind the AKT protein has been performed after the generation of a pharmacophore model based on the experimental structure of AKT1 complexed with IQO, a well-known inhibitor. The compounds resulted as being most suitable from the screening have been further investigated by molecular docking, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis and toxicity profiles. Two compounds selected at the end of the computational analysis, i.e., ZINC2429155 (also named STL1) and ZINC1447881 (also named AC1), have been tested in an experimental assay, together with IQO as a positive control and quercetin as a negative control. Only STL1 clearly inhibited AKT activation negatively modulating the PI3K/AKT pathway.

In silico insights into the identification of potential novel angiogenic inhibitors against human VEGFR-2: a new SAR-based hierarchical clustering approach.

In this study, binding efficiency of new pyrrolopyrimidine structural analogs against human vascular endothelial growth factor receptor-2 (VEGFR-2) were elucidated using integrated in silico methods. Optimized high-resolution model of VEGFR-2 was generated and adopted for structure-based virtual screening approaches. Pyrrolopyrimidine inhibitor (CP15) associated compounds were screened from PubChem database and subjected to virtual screening and comparative docking methods against the receptor ligand-binding domain. Accordingly, high efficient compounds were clustered with similarity indices through PubChem structure cluster module using single-linkage algorithm. Moreover, pharmacokinetics including drug metabolism activities of high-binding leads under investigation was portrayed using ADMET and similarity ensemble analysis. Optimal energy orientations of the selected protein model have been shown to be reliable, and highly recommended for screening and docking studies. Docking and clustering strategies were shown that nineteen candidates as most effective binders for VEGFR-2 than CP15, and are grouped as three classes. Lys868, Glu885, Cys919, His1026, Arg1027, Asp1046, and Gly1048 residues were predicted as novel hotspot residues, and participate in H-bonds, π-cation, π-stacking, halogen bonds, and salt-bridges formation with ligands. These additional bonds are contributing extent stability that holds the receptor structure at flexible state, this make difficult to any further conformational changes for evoking angiogenic signals. The ADMET and similarity ensemble analysis results were strongly indicated that thirteen candidates as best ligands for angiogenesis targets. Altogether, these findings indicate potential angiogenic templates and their binding levels with VEGFR-2; sorted viewpoints could be useful as a promising way to describe potential angiogenesis inhibitors with related molecular targets.

Antileishmanial potential of fused 5-(pyrazin-2-yl)-4H-1,2,4-triazole-3-thiols: Synthesis, biological evaluations and computational studies.

A series of newer 1,2,4-triazole-3-thiol derivatives 5(a-m) and 6(a-i) containing a triazole fused with pyrazine moiety of pharmacological significance have been synthesized. All the synthesized compounds were screened for their in vitro antileishmanial and antioxidant activities. Compounds 5f (IC50=79.0µM) and 6f (IC50=79.0µM) were shown significant antileishmanial activity when compared with standard sodium stibogluconate (IC50=490.0µM). Compounds 5b (IC50=13.96µM) and 6b (IC50=13.96µM) showed significant antioxidant activity. After performing molecular docking study and analyzing overall binding modes it was found that the synthesized compounds had potential to inhibit L. donovani pteridine reductase 1 enzyme. In silico ADME and metabolic site prediction studies were also held out to set an effective lead candidate for the future antileishmanial and antibacterial drug discovery initiatives.

Investigating the anti-cancer compounds from Calliandra harrisii for precision medicine in pancreatic cancer via in-silico drug design and GC-MS analysis.

Pancreatic cancer is a fatal illness caused by mutations in multiple genes. Pancreatic cancer damages the organ that helps in digestion, resulting in symptoms including fatigue, bloating, and nausea. The use of medicinal plants has been crucial in the treatment of numerous disorders. The medicinal plant Calliandra Harrisi has been widely exploited for its possibilities in biology and medicine. The current study aimed to assess the biopotential of biologically active substances against pancreatic cancer. The GC-MS data of these phytochemicals from Calliandra Harrisi were further subjected to computational approaches with pancreatic cancer genes to evaluate their potential as therapeutic candidates. Molecular docking analysis revealed that N-[Carboxymethyl] maleamic acid is the leading molecule responsible for protein denaturation inhibition, having the highest binding affinity of 6.8 kJ/mol among all other compounds with KRAS inflammatory proteins. Furthermore, ADMET analysis and Lipinski's rule validation were also performed revealing its higher absorption in the gastrointestinal tract. The results of the hepatotoxicity test demonstrated that phytochemicals are non-toxic, safe to use, and do not cause necrosis, fibrosis, or vacuolar degeneration even at excessive levels. Calliandra Harrisi has phytoconstituents that have a variety of pharmacological uses in consideration.

Antibacterial and Antibiofilm Potential of Chlorophyllin Against Streptococcus mutans In Vitro and In Silico.

BACKGROUND: Streptococcus mutans is a leading causative agent of dental caries and exerts pathogenicity by forming biofilms. Dental caries continues to be a significant public health issue worldwide, affecting an estimated 2.5 billion people, showing a 14.6% increase over the past decade. Herein, the antibacterial potential of Chlorophyllin extracted from Spinacia oleracea was evaluated against biofilm-forming S. mutans via in vitro and in silico studies. METHODOLOGY: The antimicrobial activity of chlorophyllin extract against S. mutans isolates was tested using the agar well diffusion method. Chlorophyllin extract was also tested against biofilm-forming isolates of S. mutans. Chlorophyllin was docked with the antigen I/II (AgI/II) protein of S. mutans to evaluate its antimicrobial mechanism. The chemical structure and canonical SMILES format of Chlorophyllin were obtained from PubChem. Additionally, adsorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses of Chlorophyllin were performed using ADMETlab 2.0 to assess its pharmacokinetic properties. RESULTS: An agar well diffusion assay revealed that all S. mutans isolates were susceptible to Chlorophyllin extract and showed a variety of inhibition zones ranging from 32 to 41 mm. Chlorophyllin reduces the biofilm strength of four isolates from strong to moderate and six from strong to weak. The antibiofilm potential of Chlorophyllin was measured by a reduction in the number of functional groups observed in the Fourier Transform Infrared Spectrometer (FTIR) spectra of the extracellular polymeric substance (EPS) samples. Chlorophyllin showed binding with AgI/II proteins of S. mutans, which are involved in adherence to the tooth surface and initiating biofilm formation. The ADMET analysis revealed that the safety of Chlorophyllin exhibited favorable pharmacokinetic properties. CONCLUSIONS: Chlorophyllin stands out as a promising antibacterial and antibiofilm agent against biofilm-forming S. mutans, and its safety profile highlights its potential suitability for further investigation as a therapeutic agent.

Comparative In Vitro and In Silico Analyses of Phytochemicals From Butea monosperma for Wound-Healing Potential in Human Cells.

Aim The objective of this study is to investigate the phytochemicals present in Butea monosperma and assess their potential for healing wounds using a computational comparative method. Materials and methods The phytochemical substances derived from B. monosperma were examined using a phytochemical test, Fourier-transform infrared (FTIR) spectroscopy, and gas chromatography-mass spectroscopy (GCMS). The chemical structures of these substances were investigated in silico using computational techniques to predict their wound-healing capacity. The molecular docking tests evaluate the binding strengths of the phytochemicals to specific proteins that play a major role in wound-healing mechanisms. The pharmacokinetic features of the substances were evaluated by analyzing their ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiles. Results The computer analysis found several phytochemicals from B. monosperma that bind strongly to the proteins for wound healing: compounds such as hexanoic acid, 2,7-dimethyloct-7-en-5-yn-4-yl ester, 1,3,5-pentanetriol, 3-methyl-, and 2-butyne-1,4-diol. The ADMET analysis indicated favorable pharmacokinetic properties for the majority of the identified compounds, with low predicted toxicity. Conclusion Based on the in silico analysis, the phytochemicals in B. monosperma possess significant potential for use in wound-healing applications. These findings required additional in vitro and in vivo studies to confirm the effectiveness and safety of these drugs for improving wound healing. This study emphasizes the potential of B. monosperma as a source of innovative medicinal substances for wound care.

Insilico assessment of hesperidin on SARS-CoV-2 main protease and RNA polymerase: Molecular docking and dynamics simulation approach.

The present study uses molecular docking and dynamic simulations to evaluate the inhibitory effect of flavonoid glycosides-based compounds on coronavirus Main protease (Mpro) and RNA polymerase. The Molegro Virtual Docker (MVD) software is utilized to simulate and calculate the binding parameters of compounds with coronavirus. The docking results show that the selected herbal compounds are more effective than those of chemical compounds. It is also revealed that five herbal ligands and two chemical ligands have the best docking scores. Furthermore, a Molecular Dynamics (MD) simulation was conducted for Hesperidin, confirming docking results. Analysis based on different parameters such as Root-mean-square deviation (RMSD), Root mean square fluctuation (RMSF), Radius of gyration (Rg), Solvent accessibility surface area (SASA), and the total number of hydrogen bonds suggests that Hesperidin formed a stable complex with Mpro. Absorption, Distribution, Metabolism, Excretion, And Toxicity (ADMET) analysis was performed to compare Hesperidin and Grazoprevir as potential antiviral medicines, evaluating both herbal and chemical ligand results. According to the study, herbal compounds could be effective on coronavirus and are admissible candidates for developing potential operative anti-viral medicines. Hesperidin was found to be the most acceptable interaction. Grazoprevir is an encouraging candidate for drug development and clinical trials, with the potential to become a highly effective Mpro inhibitor. Compared to RNA polymerase, Mpro showed a greater affinity for bonding with Hesperidin. van der Waals and electrostatic energies dominated, creating a stable Hesperidin-Mpro and Hesperidin-RNA polymerase complex.

Using Quality by Design Tools to Study Gel Formulation from Brassica juncea Leaves and Conducting its In vitro, In vivo, Molecular Docking, and ADMET Analyses.

INTRODUCTION: This research aims to create a gel formulation of Brassica juncea leaf extract and assess its anti-inflammatory properties using an in silico study. The anti-inflamma-tory activity has been compared with Diclofenac molecules in PDB id: 4Z69. Further, the Ab-sorption, Distribution, Metabolism, Excretion, and Toxicity analysis has been performed to en-sure the therapeutic potential and safety of the drug development process. The Quality by De-sign tool has been applied to optimize formulation development. METHODS: The extracted gel is characterized by performing Fourier transformer infrared, zeta potential, particle size, Scanning Electron Microscope, and entrapment efficiency. Further, the formulation is evaluated by examining its viscosity, spreadability, and pH measurement. An In-vitro study of all nine extract suspensions was conducted to determine the drug contents at 276 nm. RESULTS: The optimized suspension has shown the maximum percentage of drug release (82%) in 10 hours of study. Animal study for anti-inflammatory activity was performed, and results of all five groups of animals compared the % inhibition of paw edema at three hours; gel (56.70 %), standard (47.86 %), and (39.72 %) were found. CONCLUSION: The research could conclude that the anti-inflammatory activity of gel formulation is high compared to extract, and a molecular docking study validates the anti-inflammatory ther-apeutic effects. ADMET analysis ensures the therapeutic effects and their safety.

Phyto-pharmacological and computational profiling of Bombax ceiba Linn. Leaves revealed pharmacological properties against oxidation, hyperglycemia, pain, and diarrhea.

The present study aimed to conduct phytochemical and pharmacological profiling of methanolic crude extract of leaves of Bombax ceiba Linn. via experimental and computational approaches. Six secondary metabolites were isolated chromatographically, and the structures were elucidated by extensive analyses of high-resolution 1H and 13C NMR data. The separated compounds were characterized as ß-sitosterol (1), ß-amyrin (2), ß-amyrin acetate (3), ß-amyrin palmitate (4), ß-amyrone (5), and isoscopoletin (6). DPPH free radical scavenging assay, tail-tipping method, writhing assay, and castor oil-induced diarrheal mice methods, respectively, were used to assess the antioxidant, hypoglycemic, analgesic, and anti-diarrheal activities of the leaf extract of B. ceiba plant species. The study observed significant reductions (p < 0.05) in the level of blood glucose at 30, 60, 120, and 180 min following the administration of the crude extracts (200 mg/kg body weight (bw) and 400 mg/kg bw). These reductions occurred in a time-dependent manner. Additionally, both doses of the investigated extracts exhibited significant (p < 0.05) central and peripheral analgesic effects compared to morphine (2 mg/kg bw) and diclofenac sodium (50 mg/kg bw), respectively. Furthermore, the 400 mg/kg bw extract demonstrated anti-diarrheal activity, reducing 54.17 % of diarrheal episodes in mice compared to loperamide with 70.83 % inhibition. The computational investigations yielded results consistent with existing in vivo findings. The results obtained from molecular docking showed that the isolated compounds had a better or comparable binding affinity to the active binding sites of the glutathione reductase enzyme, mu-opioid receptor, cyclooxygenase 2 (COX-2), glucose transporter 3 (GLUT 3), and kappa opioid receptor. These findings may indicate that the compounds isolated from the B. ceiba plant species have antioxidant, analgesic, hypoglycemic, and anti-diarrheal, properties. Consequently, it was inferred that the plant B. ceiba might be beneficial in dealing with oxidation, diarrhea, hyperglycemia, and pain. Nonetheless, further investigations are necessary to perform thorough phytochemical profiling and elucidate the exact mechanistic ways of the crude extract and the isolated phytoconstituents.

Exploration of comprehensive marine natural products database against dengue viral non-structural protein 1 using high-throughput computational studies.

Dengue virus (DENV) non-structural protein 1 (NS1) is a versatile quasi-protein essential for the multiplication of the virus. This study applied high-throughput virtual screening (HTVS) and molecular dynamics (MD) simulation to detect the potential marine natural compounds against the NS1 of DENV. The structure of the NS1 protein was retrieved from Protein Data Bank with (PDB ID: 4O6B). Missing residues were added using modeler software. Molecular operating environment (MOE) programme was used to prepare the protein before docking. Virtual screening was performed on PyRx software to identify natural compounds retrieved from Comprehensive Marine Natural Products Database (CMNPD) against the NS1 protein, and best-docked compounds were examined by molecular docking and molecular dynamic (MD) simulation. Out of 31,561 marine compounds, the top 10 compounds showed docking scores lesser than -8.0 kcal/mol. One of the best hit compounds, CMNPD6802, was further analyzed using MD simulation study at 100 nanoseconds and Molecular Mechanics with Generalized Born and Surface Area Solvation (MM/GBSA). Based on its total binding energy, determined using the MM/GBSA approach, CMNPD6802 was ranked first. Its pharmacokinetic properties concerning the target protein NS1 were also evaluated. The results of the MD simulation showed that CMNPD6802 remained in close contact with the protein throughout the activation period, mapped using principal component analysis. These findings suggest that CMNPD6802 could serve as an NS1 inhibitor and may be a potential candidate for treating DENV infections.Communicated by Ramaswamy H. Sarma.

Imaging metabolic mechanisms and the binding behavior of nutrients/transporters of edible Matricaria flowers VOCs.

To promote the consumption of flowers and to utilize the nutritional value of proteins, the efficacy of the beneficial components of flowers has been intensively studied. Anthemis nobilis was used as the study object, and all its volatile components (VOCs) were fingerprinted using headspace solid-phase micro-extraction gas-mass spectrometry (HS-SPME/GC-MS). GC-MS fingerprints of five parts of Anthemis nobilis were established using three proteins, bovine lactoferrin (BLF), bovine lactoglobulin (ß-Lg), and human serum albumin (HSA), as nutrient transporters. The interactions between the volatile components from different parts of the mother chrysanthemum plant and the nutrient/transport proteins were investigated. The results of fingerprinting showed that the flavor components were dominated by alkenes. In addition, this study revealed that among the three nutrient transporters, the strongest binding to the adsorbed volatile components was HSA, followed by BLF, and ß-Lg was second. In addition, a characteristic molecule, camphene, was screened. Integrated molecular simulation using fluorescence spectroscopy was used to validate the results of the interaction of the nutrient/transport proteins systems with characteristic molecule. The properties of the characteristic molecules such as absorption, distribution, metabolism, excretion and toxicity in vivo were analyzed using ADMET to provide a theoretical basis for the preparation of flower-flavored dairy products.

Molecular Docking and ADMET Analysis Strategy-Based Stability Indicating RP-HPLC-PDA Method Development and Validation of Toremifene.

BACKGROUND: The purpose of this research is to develop an analytical method and validate it according to ICH guidelines for the estimation of Toremifene by RP-HPLC-PDA with molecular docking and ADMET analysis. From molecular docking, it came to know the receptor affinity specifically to estrogen receptors (ERα and ERß), which are responsible for cancer therapy. ADMET analyses secure its therapeutic potential as well safety of the drug. METHODS: An isocratic method has developed by RP-HPLC-PDA (AGILENT 1100) with symmetry of 100 mm x 4.6 mm x 5 µm particle size C18 column and optimise mobile phase is methanol: 0.1% OPA (orthophosphoric acid) water ratio of 43:57% v/v. Under different conditions like acidic, alkaline, oxidative, and neutral environments, toremifene was tested for degradation. RESULTS: The developed method is validated in accordance with ICH guidelines. A calibration curve with an r2 value of 0.9987 has been prepared across the range of 10 to 50 µg/ml with five standard dilutions. The retention time of the drug is 5.575 minutes. The validation results are system suitability (%RSD-0.76), inter-day precision (%RSD 0.14-0.29), intraday precision (%RSD 0.08-0.34), accuracy (%RSD 0.16-0.96), and robustness (%RSD 0.16-0.35). In different intended conditions, four peaks are in 1 N HCl, two peaks in 1 N NaOH, three peaks in 10% H2O2 (1hr), and one peak in neutral. CONCLUSION: Toremifene, a Selective Estrogen Receptor Modulator (SERM), Drug pharmacokinetic properties and receptor binding affinity results are helpful in designing the analytical method. Developing the RP-HPLC-PDA method is found to be novel, simple and precise. It could be used for testing toremifene in bulk and pharmaceutical tablet dosage forms in quality control, as well as stability tests.