AutoDock Research Articles

Mechanism exploration of SanShi ShengXin Ointment in the treatment of pressure ulcers based on network pharmacology and molecular docking.

To explore the active ingredients, prospective targets, and action mechanisms of SanShi ShengXin Ointment in the treatment of pressure ulcers (PU) based on the network pharmacology technique and molecular docking technology. The active ingredients and action targets of Sanshishengxin Ointment were searched through the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform. The PU-related targets were retrieved from the GeneCards and DisGeNET databases. The intersection target genes of disease and drugs were obtained. The "disease-drug-active ingredient-target" was constructed using Cytoscape software. The intersection target genes were imported into the String database to construct a protein-protein interaction network for gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The Auto Dock software was used for relevant molecular docking. A total of 78 active ingredients of SanShi ShengXin Ointment were obtained, corresponding to 539 target genes. There were 5896 PU-related target genes, and 373 intersection target genes of disease and drugs were obtained, such as STAT3, TP53, JUN, MAPK3, CTNNB1, involving PI3K-Akt, TNF, MAPK, and other related signaling pathways. Based on network pharmacology and molecular docking analyses, this study demonstrates that SanShi ShengXin Ointment can treat PU through multicomponent, multitarget, and multipathway. .

Is Daclatasvir a suitable substitute for Amphotericin B in the treatment of Mucormycosis when Amphotericin B is scarce?

Mucormycosis has been infesting the universe for a while back, often with no prompt treatments. The disease devastation is spreading at an alarming rate. Many researchers are still hoping for a good potential drug that could help the healthcare system in this tussle. Molecular docking is an in silico tool that has gained popularity over the last few decades. Knowing the mechanism of enzymatic action is aided by imitating membrane protein actions in binding ligands. The aim of this perspective is to determine whether an existing drug, daclatasvir, has antifungal activity. The primary objective of this in silico study was to investigate the potential effects of the binding affinity of daclatasvir with the crucial protein (1XFF) of mucormycosis, as well as the binding pattern of the active site amino acids with the drug molecule. To calculate the binding affinity of daclatasvir to the fungal protein 1XFF, Auto Dock Vina was used for molecular docking studies. The CDOCKER protocol was used to determine the receptor-ligand interaction by configuring various parameters. The docking energy of the ligand (daclatasvir) on the protein (1XFF) was found to be -16.7216 kcal/mol, while the interaction energy was found to be - 42.1314 kcal/mol. The binding pattern completely alters the dynamics of the protein, resulting in the breakdown of the fungal wall. The vital protein (1XFF) of Rhizopus oryzae is proposed as a possible protein target for the non-structural protein 5A inhibitor/antiviral drug daclatasvir in this study.

“Molecular Docking Analysis Of Alpha-Terpineol Against Matrix Metalloproteinases”

Objectives: The process of wound healing is crucial and complex within the human body, involving various enzymes. Increased concentrations of matrix metalloproteinases (MMPs) at the wound site lead to slowdown in the healing process. Small bioactive compounds produced from natural sources can be used to down-regulate or inhibit these over expressed MMPs. Alpha-terpineol, a mono-terpenoid alcohol with a monocyclic structure, is present in vitex negundo linn leaf, pemus boldus leaf, cajeput oil, coriander oil, and pine oil. It exhibits diverse biological uses, serving as an antioxidant, anticancer, anticonvulsant, antiulcer, anti-inflammatory, antihypertensive, and anti-nonciceptive agent. The work aims to use molecular docking to understand how alpha-terpineol binds to MMPs. Materials and Methods: The MMPs was obtained from RCSB database and the alpha-terpineol was obtained from Pubchem. The Auto Dock software was used to create a molecular docking of alpha-terpineol activity on MMPs. Alpha-Terpineol binds to MMPs receptors. Auto Dock Vina was used to examine the binding box-related files, including a PDBQT file and PYMOL software was then used to analyze the receptor and ligand PDBPT files. Result: Docking tests revealed that alpha-terpineol has a great binding affinity for all four MMPs tested. MMPs 3, 8, and 12 had free binding energies of around -9.1, -10.5, and -9.7kcal/mol, respectively. Conclusion: Therefore, alpha-terpineol can be employed to regulate the function of matrix metalloproteinases and facilitate the process of wound healing.

Discussion on the mechanism of Danggui Sini decoction in treating diabetic foot based on network pharmacology and molecular docking and verification of the curative effect by meta-analysis.

The main active components and mechanism of Danggui Sini decoction (DSD) in treating diabetic foot (DF) were studied and verified by network pharmacology and molecular docking. Evidence-based medicine was used to prove its efficacy. The TCMSP systematic pharmacology platform screened out DSD's practical components and targets-screening disease targets in GeneCards database, using Cytoscape 3.7.2 to draw DSD-active ingredient-target network diagram, and drawing the protein interaction network diagram through STRING database. The Metascape platform was used to analyze the GO function enrichment and KEGG signal pathway. The molecular docking experiment was carried out by using Auto Dock vina 4.2. The related literature on DSD in treating DF in China Zhiwang, Wanfang, Weipu, and China Biomedical Literature Database was searched. The literature was screened, data was extracted, and quality was evaluated according to the inclusion and exclusion criteria. Then, a meta-analysis was performed using RevMan 5.3 software. A total of 256 targets of all effective components of DSD were obtained. Among 1,272 disease targets, there are 113 common targets. The GO analysis received 6,179 entries, and the KEGG pathway enrichment analysis found 251 related pathways. The molecular docking results of the main targets of diabetic foot and the active substances of DSD all showed a high docking activity. The meta-analysis included six literature, all of which were randomized controlled experiments. The quality grade of the literature was C, and the results showed that the total effective rate of clinical efficacy in the experimental group was significantly higher than that in the control group. DSD may treat DF by participating in biological processes such as cell proliferation regulation, inflammatory reaction, oxidative stress reaction, and promotion of angiogenesis. DSD treats DF through AKT1, TP53, IL6, TNF, VEGFA, and other targets. DSD plays a role in treating DF mainly through the AGE-RAGE signaling pathway and PI3K-AKT signaling pathway. The molecular docking results of AKT1, TP53, IL-6, TNF, and VEGFA with the active substances of DSD show that they all have a high docking activity; among them, VEGFA has a higher docking activity. Compared with conventional treatment, DSD has a high effective rate, short wound healing time, large wound healing area, and high ABI index.

Molecular Docking Based Predictive Study of Bougainvillea Glabra against Mtorc1 Protein for the Treatment of Diabetic Nephropathy: Network Pharmacology

Background: The decline in kidney function experienced by people with type 1 and type 2 diabetes who are chronically ill is known as diabetic nephropathy (DN) or diabetic kidney disease. The condition is known to progress in a number of stages and is related to blood pressure and glycemic management. Nevertheless, despite strict blood sugar management, the prevalence of chronic kidney disease (CKD) in diabetic patients has not decreased over the past 20 years, which has led to the discovery of new risk factors for the illness's development. The medical characteristics of the Paper Flower, Bougainvillea spectabilis, include anti-inflammatory, anti-hepatotoxic, anti-inflammtory, anti-hyperlipidemic, antibacterial, antioxidant, and antiulcer capabilities. Alkaloids, flavonoids, glycosides, phenolics, phytobannins, quinones, saponins, tannins, and terpenoids are examples of phytoconstituents that have been claimed to have medicinal characteristics. Method: In the current study, a molecular docking technique was used to try and identify mTORC1protein inhibitors. A grid-based docking strategy was used to determine the binding using the Auto Dock software. Merck Molecular Force Field was used to build the 2D structures of compounds, convert them to 3D, and then energetically reduce them up to arms gradient of 0.01. (MMFF). Result: The molecular docking of Ferulic acid & Gallic acid with mTORC1 protein showed binding energy (Kcal/mol) -5.37 & -4.56 respectively. Conclusion: Theoretically, all the ligand molecules have shown encouraging docking score. The docking result of ferulic acid revealed that their docking scores was -5.37 kcal mol–1, and it can be predicted as good inhibitor of mTORC1 protein and thereby prevents dysregulation of intracellular protein synthesis and the metabolic balance along with decreasing oxidative stress on the kidney.

Anti-Diabetic Evaluation Of The Traditional Siddha Polyherbal Formulation - Madhu Mukthi Kudineer Chooranum By In Silico Analysis

Background: From ancient times Siddha medicines have been proven to treat a wide range of communicable and noncommunicable diseases. In India, the number of people affected with diabetes is increasing drastically and it is considered as an epidemic. Purpose: To assess the anti-diabetic activity of the active compounds of the polyherbal formulation – Madhu Mukthi Kudineer Chooranum (MKC) by docking against potent enzymes involved in diabetes mellitus by in silico method. Methods: The major target enzymes Dipeptidyl peptidase, Glycogen synthase kinase - 3β, Alpha-glucosidase and Alpha-amylase were docked against the 10 active compounds present in the MKC using Auto Dock tools. Conclusion: The strong interactions between the target enzymes and the active compounds proved the anti-diabetic efficacy of the MKC formulation. Thus, the intake of MKC has potential benefits in the treatment of Type II Diabetes Mellitus.

Vibrational spectra, molecular structure, electronic, pharmaceutical and bonding nature of (4S)-4-(3,4-dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline-7,8-diol - anti hypertension agent

Several factors, including environment, behaviours, and heredity, influence the development of hypertension. The title compound dopamine D1 receptor agonist named (4S)-4-(3,4-dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline-7,8-diol (4S4D4T) is one of the most important neurotransmitters associated with numerous neural disorders. Using DFT and quantum chemical simulations, the vibrational, electrical, and structural possessions of the heading compound were predicted. To carry out the quantum computational investigations, a highly compatible method entitled B3LYP basis set was adopted. Vibrational Modes of functional groups with PED values were calculated using VEDA software to compute geometric dimensions and assign fundamental vibrations. Using gas and solvent phases, MEP differentiates between nucleophilic and electrophilic sites and creates distribution for the charge of the molecules. The observed wavelength with (TDSCF) UV–Vis spectra for the various solvents phases were compared. The NBO approach provides an understanding of the electron delocalization that results from hyperconjugation. FUKUI analysis is used to determine the area of site reaction. Electron density's topological analysis was carried out using the QTAIM theory. The ADME (Absorption, Distribution, Metabolism, Excretion) profiles are produced with the Swiss ADME online tool. In summary, this dissertation offers a thorough examination that evaluates the impact of particular pharmaceuticals on solvation and enzyme efficiency using a combination of spectral and quantitative computing methodologies. Therefore, plans for further research can profit immensely by the information gathered. The results of protein-ligand docking using the Auto Dock method with various proteins suggest that the molecule has pharmaceutical properties against receptors.

Betulinic and ursolic acids from Nauclea latifolia roots mediate their antimalarial activities through docking with PfEMP-1 and PfPKG proteins

BackgroundChemotherapies target the PfEMP-1 and PfPKG proteins in Plasmodium falciparum, the parasite that causes malaria, in an effort to prevent the disease’s high fatality rate. This work identified the phytochemical components of Nauclea latifolia roots and docked the chemical compounds against target proteins, and examined the in vivo antiplasmodial effect of the roots on Plasmodium berghei-infected mice.MethodsStandard protocols were followed for the collection of the plant’s roots, cleaning, and drying of the roots, extraction and fraction preparation, assessment of the in vivo antiplasmodial activity, retrieval of the PfEMP-1 and PfPKG proteins, GCMS, ADME, and docking studies, chromatographic techniques were employed to separate the residual fraction’s components, and the Swis-ADME program made it possible to estimate the drug’s likeness and pharmacokinetic properties. The Auto Dock Vina 4.2 tool was utilized for molecular docking analysis.ResultsThe residual fraction showed the best therapeutic response when compared favorably to amodiaquine (80.5%) and artesunate (85.1%). It also considerably reduced the number of parasites, with the % growth inhibition of the parasite at 42.8% (D2) and 83.4% (D5). Following purification, 25 compounds were isolated and characterized with GCMS. Based on their low molecular weights, non-permeation of the blood–brain barrier, non-inhibition of metabolizing enzymes, and non-violation of Lipinski’s criteria, betulinic and ursolic acids were superior to chloroquine as the best phytochemicals. Hence, they are lead compounds.ConclusionIn addition to identifying the bioactive compounds, ADME, and docking data of the lead compounds as candidates for rational drug design processes as observed against Plasmodium falciparum target proteins (PfEMP-1 and PfPKG), which are implicated in the pathogenesis of malaria, the study has validated that the residual fraction of N. latifolia roots has the best antiplasmodial therapeutic index.

A network pharmacology method explores the molecular mechanism of Coptis chinensis for the treatment of Alzheimer's disease.

To predict the molecular mechanisms of action of Coptis chinensis in the treatment of Alzheimer's disease using network pharmacology. The active ingredients and targets of Coptis chinensis were obtained from the Traditional Chinese Medicine System Pharmacology Database. Target information for Alzheimer's disease was screened using the GeneCard and OMIM databases. The Venn diagram tool was used to identify the intersecting targets of Coptis chinensis and Alzheimer's disease. The obtained target information was entered into the STRING database to construct a protein-protein interaction network. The R language was used to perform Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses of significant targets. Auto Dock Vina software was used for molecular docking. Fourteen effective active ingredients and 158 key targets associated with Coptis chinensis were identified. There were 1113 targets related to Alzheimer's disease genes. A drug-component-disease-target network was constructed and 84 key targets were identified for the treatment of Alzheimer's disease by Coptis chinensis. The main signaling pathways were the PI3K-Akt, AGE-RAGE, MAPK, HIF-1, TNF, and relaxin signaling pathways. The molecular docking results showed that berberine has a high affinity for Alzheimer's Disease. Coptis chinensis could play a multi-target and multi-pathway role against Alzheimer's disease, which has guiding significance for clinical research.

Molecular Docking Studies of Thiazolidinediones on Receptor for Advanced Glycation End Products (RAGE)

Background: Advanced glycation end products (AGE), are abnormal glycation of molecular proteins and nucleic acid, and its interaction with receptors for advanced glycation end products (RAGE) culminates in metabolic, neurodegenerative, and lifestyle disorders. Thiazolidinediones are insulin sensitizers with anti-glycation activity and are currently used clinically as anti-diabetic drugs. Research rationale: Studies show that thiazolidinediones also exhibit antioxidant and antiglycation activity; hence we proposed that this anti-glycation activity of thiazolidinedione may be due to its anti-RAGE action, thus preventing further RAGE-AGE interaction. Purpose of the study: Aim of the current study is to assess In-silico anti-RAGE activity of nine thiazolidinediones namely pioglitazone, rosiglitazone, ciglitazone, darglitazone, englitazone, netoglitazone, rivoglitazone, troglitazone and balaglitazone with RAGE. Materials and Methods: Nine thiazolidinediones namely, pioglitazone, rosiglitazone, ciglitazone, darglitazone, englitazone, netoglitazone, rivoglitazone, troglitazone and balaglitazone were downloaded from PubChem database. RAGE protein was downloaded from the PDB database. The nine thiazolidinediones were docked with RAGE protein using Auto Dock software and interaction parameters were studied. Result: All nine thiazolidinediones showed acceptable binding energy below (-8Kcal/mol) with 1-5 hydrogen bonds. Rosiglitazone exhibits the highest binding energy (-8.24Kcal/mol) with 2 hydrogen bonds for RAGE. Troglitazone exhibits the lowest binding energy (-9.95Kcal/mol) with 3 hydrogen bonds for RAGE. Conclusion: Thus our Insilco docking studies of thiazolidinedione derivatives with RAGE conclude that these nine thiazolidinedione derivatives exhibit anti-glycation activity by direct interaction with receptors of RAGE. Thus, this work warrants future preclinical studies to claim its RAGE receptor modulation activity.

Efficacy of fumigant compounds from essential oil of feverfew (Chrysanthemum parthenium L.) against maize weevil (Sitophilus zeamais Mots.): Fumigant toxicity test and in-silico study

Post-harvest insects are among the significant problems in the agricultural sector. The most accessible tools available for managing post-harvest arthropod-pests are fumigants because of the convenience of their applications and fast action in disinfecting. This study aimed to examine the fumigant toxicity of essential oil (EO) against maize weevil and identify the specific fumigants among the major components. The EO was extracted from aerial part of Chrysanthemum parthenium L. using Clevenger apparatus and was tested for fumigant toxicity. GC-MS was used to determine the chemical composition of EO. The major components were identified and screened virtually using Auto dock vina 1.2. in PyRx 0.8 platform. Dm AChE PDB ID: 6XYY was used as a target for molecular docking and malathion and pirimiphusmethyl were used as a reference for comparison. From the results of binding affinities, most of the major EO components showed better fumigant activity than the reference fumigants. More specifically 1,6-dioxaspiro[4,4]non-ene, b-farensen, bornyl-tiglate, g-terpinene, p-cymene, bornyl-acetate, bornyl-isovalerate, terpinen-4-ol, trans-chrysanthenyl-acetate and a-phellandrene were found to be effective fumigants against maize weevil. The above findings suggest that the EO of the aerial part of C. parthenium can be a potential candidate for the development of novel natural fumigants for stored products.
 KEY WORDS: Essential oil, Fumigants, Insecticides, Binding affinity, Maize weevil
 Bull. Chem. Soc. Ethiop. 2024, 38(2), 457-472. 
 DOI: https://dx.doi.org/10.4314/bcse.v38i2.13

Efficacy of the marine red alga Laurencia papillosa extract on alloxan stimulated hyperglycemic activity in male wistar albino rats

PurposeDiabetes mellitus, a main health concern worldwide, is one of the most common metabolic disorders characterized by insulin secretion dysfunction. Materials and methodsIn this work, dietary fibers of the ethanolic extract of Laurencia papillosa were detected at 0.1 and 0.2 g/kg body weight using gas chromatography-mass spectrometry (GC-MS). The extract was given orally once daily to male diabetic rats induced with alloxan for two weeks. The blood cholesterol levels, complete blood count, liver function, kidney function, and antioxidant enzymes were analyzed. The molecular docking was operated using Auto Dock Vina. ResultsTreatment with extracts of L. papillosa (0.1–0.2 g/kg) induced a decrease in pre-prandial and post-prandial glucose levels. 0.1 g/kg pre-prandial extract had the highest activity to reduction glucose level (48.670 ± 0.57 mg/dL). Moreover, the complete blood count, kidney function, and liver function differed slightly in the treated mice group compared to the non-treated diabetic group. Docking analyses demonstrated that most ethanolic compounds found within L. papillosa extract have minimum docking scores and high binding affinity against human pancreatic alpha-amylase (PDB: 4W93), insulin receptor (PDB:1IR3), and SIRT-6 (PDB: 3k35) ConclusionResults further suggested that the concentration of 0.1 g/kg of L. papillosa extract was more effective than 0.2 g/kg in reducing glucose levels. Our study induced that in vivo and in silico results indicated that L. papillosa extract has been a viable natural bioactive source and might be a great potential source for future antidiabetic medicine.

Scientific Validation of Flavonoids for Effective Management of Pancreatitis: In-Silico Molecular Docking

When someone develops pancreatitis, their pancreas swells up in inflammation. Pancreatic damage happens when the digestive enzymes are activated before they are discharged into the small intestine and begin attacking the pancreas. There are two types of pancreatitis: acute and chronic. Alcohol consumption and gallstones are just two of the numerous potential causes of pancreatitis. Plant medicine is an effective way to cure pancreatitis. Citrus flavonoids may offer promising bioactive molecules for treating metabolic disorders, according to some research. Hesperidin is widely consumed in the Western diet in this regard, mostly through the consumption of orange juice. Furthermore, since refined hesperidin is easily extracted or produced and is highly purified industrially, it is inexpensively available commercially. The Western diet contains little eriodictoyl, which is mostly found in lemons and is commercially available. Method: In the current work, NF-kβ receptor inhibitors were sought after using a molecular docking approach. The binding was determined by the Auto Dock software utilizing a grid-based docking method. Compounds' 2D structures were constructed using the chem sketch, converted to 3D, and then energetically reduced up to an arms gradient of 0.01. (MMFF). Result: Hesperetin and Eriodictoyl found to be effective anti-pancreatitis agent effectively binds to be target protein NF-kβ receptor with binding energy -6.9 & -6.7 kcalmol-1 for hesperetin & eriodictoyl respectively. Conclusion: It was discovered through a computationally based docking analysis that both lead compounds exhibit strong NF-KB receptor inhibiting effects. The results demonstrated a promising docking score and lead molecule's pattern of binding to the target protein's active region with strong covalent bonding. The synergistic impact of hesperetin & eriodictoyl is ability to heal pancreatitis.

Solute solvent interaction study on 9,9-dihydroxynanoic acid by DFT, IR, Raman, UV, MEP, quantum parameters and docking studies

Density functional quantum mechanical research yield a comprehensive theoretical approach on the selected organic molecule of 9,9-dihydroxynanoic acid. The DFT approach is implemented to optimise the molecular structure. The geometrical parameters of molecule were calculated. The vibrational spectrum studies were done with FT-IR and FT-Raman and their results were investigated. VEDA software is utilised to simulate PED for the basic vibrational frequencies in order to find all the vibration modes. UV–Vis analysis is performed for the gaseous phase and on solvent phases such as water, ethanol, ethyl ethanoate, acetone, and DMSO by TD-DFT-B3LYP with 6-311++G (d,p), and band gap energies are calculated. FMO investigations reported analysing the compound energy gap, softness, hardness, and electrophilicity index in gaseous phase along with a variety solvent phase. To further understand the molecule's reactive areas, Mulliken atomic charge evaluation, Fukui functions, and dual descriptors were conceptually investigated. The electro static MEP map of the compound in distinct solvent phases is provided in order to comprehend the molecular shape, size, and reactive region. The molecule's hyperpolarizability is observed to be 201.8 a.u for gas, 146.6 a.u for acetone, 138.9 a.u for DMSO, 136.3 a.u for water, and 169.8 a.u for ethyl ethanoate, will supports the molecule is good NLO material. The donor acceptor interaction has been explored so as to explain the intramolecular hyper conjugative interaction and stability. To understand the topology Multiwfn analysis like ELF, LOL and ALIE were done. The E.coli proteins are downloaded from the PDB database and fictitiously docked with our selected ligand molecule using Auto Dock software to determine hydrogen bonding and binding energy.

MOLECULAR DOCKING STUDY OF EPIGALLOCATECHIN GALLATE ON FLT3 IN COMPLEX WITH GILTERITINIB FOR ANTICANCER ACTIVITY

Objective: The aim of the study was to predict the binding affinity and interaction patterns between EGCG and FLT3 in complex with gilteritinib using molecular docking simulations. stabilization of the EGCG-FLT3-gilteritinib complex. Methods: The crystal structure of FLT3 in complex with gilteritinib was downloaded from the Protein Data Bank (PDB) database. Epigallocatechin gallate (EGCG) was obtained from the PubChem database. Auto Dock 8 software was utilized for the molecular docking study. The docking results are analyzed to identify the best pose based on binding affinity, hydrogen bonding, and other favorable interactions. The Discovery Studio Visualizer or other suitable software was used to visualize the protein-ligand interactions and analyze the binding mode of EGCG within the FLT3-gilteritinib complex. Results: The best ranking for ligands binding was at run 7 with the estimated free energy of binding −7.87 kcal/mol the estimated inhibition constant (ki) was 1.69 μm. The final intermolecular energy was −11.45 kcal/mol. kcal/mol It had 12 active torsions. The redocking score using gilteritinib was used as a control for the validation of the study. The estimated free energy of binding was −7.91 kcal/mol. The estimated inhibition constant ki is 1.60 μm. It had nine active torsions. Conclusion: Comparing the various binding energies and torsions of the test compound and the control revealed that the test epigallocatechin had a perfect docking score, and it was predicted to possess comparable anti-tumor and anticancer activity.

Comprehensive In Silico Analysis of Uncaria Tomentosa Extract: Chemical Profiling, Antioxidant Assessment, and CLASP Protein Interaction for Drug Design in Neurodegenerative Diseases.

Uncaria tomentosa is a traditional medicinal herb renowned for its anti-inflammatory, antioxidant, and immune-enhancing properties. In the realm of neurodegenerative diseases (NDDS), CLASP proteins, responsible for regulating microtubule dynamics in neurons, have emerged as critical players. Dysregulation of CLASP proteins is associated with NDDS, such as Alzheimer's, Parkinson's, and Huntington's diseases. Consequently, comprehending the role of CLASP proteins in NDDS holds promise for the development of innovative therapeutic interventions. The objectives of the research were to identify phytoconstituents in the hydroalcoholic extract of Uncaria tomentosa (HEUT), to evaluate its antioxidant potential through in vitro free radical scavenging assays and to explore its potential interaction with CLASP using in silico molecular docking studies. HPLC and LC-MS techniques were used to identify and quantify phytochemicals in HEUT. The antioxidant potential was assessed through DPPH, ferric reducing antioxidant power (FRAP), nitric oxide (NO) and superoxide (SO) free radical scavenging methods. Interactions between conventional quinovic acid, chlorogenic acid, epicatechin, corynoxeine, rhynchophylline and syringic acid and CLASP were studied through in silico molecular docking using Auto Dock 4.2. The HEUT extract demonstrated the highest concentration of quinovic acid derivatives. HEUT exhibited strong free radical-scavenging activity with IC50 values of 0.113 μg/ml (DPPH) and 9.51 μM (FRAP). It also suppressed NO production by 47.1 ± 0.37% at 40 μg/ml and inhibited 77.3 ± 0.69% of SO generation. Additionally, molecular docking revealed the potential interaction of quinovic acid with CLASP for NDDS. The strong antioxidant potential of HEUT and the interaction of quinovic acid with CLASP protein suggest a promising role in treating NDDS linked to CLASP protein dysregulation.

SYNTHESIS, BIOLOGICAL EVALUATION AND DOCKING STUDIES OF NEW 5-(4-ISOPROPYL PHENYL)-1,3,4- THIADIAZOL-2-AMINE DERIVATIVES

A straightforward synthetic pathway has been developed to prepare N-acylated derivatives of 5-(4-isopropyl phenyl)-1,3,4-thiadiazol-2-yl)amines 3(a-j) by reacting 5-(4-isopropyl phenyl)-1,3,4-thiadiazol-2-amine (2) with various symmetrical acid anhydrides in pyridine solvent under refluxing conditions with good yields. This study involves simple, easy, cheap, inexpensive, and benign processes. Molecular docking investigations were done using an auto dock and found that 3i, 3h, and 3a had good binding energies with PDB ID: 5JZX. The antibacterial efficacy of compounds 3(a-j) was investigated against S. aureus and E. coli. Among all the compounds 3c, 3h & 3j showed good strength towards gram-positive and compounds 3e, 3i & 3j showed good strength on gram-negative bacteria. Further antifungal activity is done against Candida albicans. Most of the prepared compounds 3(a-j) showed good activity against tested microorganisms.

Evaluation of Phytochemicals Constituents of Gyrocarpus asiaticus Willd. and Lactuca runcinata DC for Antioxidant Activity by Molecular Docking Study

In this study, based on the molecular docking study, the antioxidant activity of phytochemicals constituents of hydroalcoholic extract of Gyrocarpus asiaticus Willd. and Lactuca runcinata DC were evaluated. For molecular docking study, ligand generation of phytochemicals constituents of Lactuca runcinata DC and Gyrocarpus asiaticus Willd. were performed by visualizing software Biovia Discovery Studio. The docking study of two proteins viz. NADPH oxidase (PDB ID 2CDU) and human carbonyl reductase–I (PDB ID 3BHI) with the identified phytochemicals constituents was done by Auto Dock Vina. Depending on the docking score, the best three compounds were selected from each plant. For physico-chemical properties prediction and toxicity of these compounds were predicted by the Swiss ADME and Orisis properties explorer.

Synthesis, Characterisation, in vitro antibacterial and in silico docking studies of Schiff bases of p-nitro benzaldehyde

Schiff base ligands have more pharamaceutical applications and are widely used in pharmaceutical industries. Herein, two kinds of Schiff base ligands were synthesized using p-nitrobenzaldehyde with (L1) 1H-1,2,4-triazol-3-amine and (L2) 1,4 phenylene diamine backbone. Synthesised ligands were characterized utilizing ultraviolet visible spectroscopy, Fourier Transform Infra-red Spectroscopy, Carbon 13C NMR and Proton 1H. Then in vitro antimicrobial activity, PASS analysis, Drug likeness and in silico docking studies of synthesized ligands (L1 and L2) were carried out. With the help of PASS and bioactive score results, docking studies were done using two different proteins (PDB ID:6D9T and PDB ID:6HZQ) by Auto dock 4.2.6 program. BNBBDA has good affinity with target protein S. aureus (PDB ID:6D9T) and PNBTAA has with protein E.coli (PDB ID:6HZQ). The findings demonstrated that the compounds are the ideal candidates for the subsequent steps of drug discovery.

In silico study of polyphenols as potential inhibitors of MALT1 protein in non-Hodgkin lymphoma.

Non-Hodgkin lymphoma (NHL) is one of the most common cancer types. Deregulated signaling pathways can trigger certain NHL subtypes, including Diffuse Large B-cell lymphoma. NF-ĸB signaling pathway, which is responsible for the proliferation, growth, and survival of cells, has an essential role in lymphoma development. Although different signals control NF-ĸB activation in various lymphoid malignancies, the characteristic one is the CARD11-BCL10-MALT1 (CBM) complex. The CBM complex is responsible for the initiation of adaptive immune response. Our study is focused on the molecular docking of ten polyphenols as potential CARD11-BCL10-MALT1 complex inhibitors, essentially through MALT1 inhibition. Molecular docking was performed by Auto Dock Tools and AutoDock Vina tool, while SwissADME was used for drug-likeness and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of the ligands. Out of 66 ligands that were used in this study, we selected and visualized five. Selection criteria were based on the binding energy score and position of the ligands on the used protein. 2D and 3D visualizations showed interactions of ligands with the protein. Five ligands are considered potential inhibitors of MALT1, thus affecting NF-ĸB signaling pathway. However, additional in vivo and in vitro studies are required to confirm their mechanism of inhibition.