Docking Score Values Research Articles

Novel europium(III), terbium(III), and gadolinium(III) Schiff base complexes: Synthesis, structural, photoluminescence, antimicrobial, antioxidant, and molecular docking studies

Three lanthanide (III) complexes, L-Eu, L-Tb, and L-Gd, were synthesized using a Schiff base ligand (H2L) composed of (2,2′-(thiophene-2,5-diylbis(methaneylyl-idene))bis(azaneylyl-idene))diphenol. Complexes with the generic formula LnL(Cl)(H2O)·xH2O, where L is the ligand, was studied using elemental analysis, spectrum analysis (IR, mass- UV–Vis), and molar conductivity. Next, the photoluminescence characteristics of the lanthanide complexes were investigated. An assessment was conducted to ascertain the antioxidant activity of the synthetic compounds compared with that of the stable free radical DPPH. The antibacterial activity of the Schiff base metal complexes was assessed against a strain of yeast as well as against a number of Gram-positive and Gram-negative bacteria. Computational studies were also performed to elucidate the mechanisms of the antimicrobial and antioxidant effects. In molecular docking, 1LL9, 6J2O, 3JPU, 2MBR, and 1HD2 crystal structures were determined as targets and the docking score values of H2L, L-Tb, L-Gd, and L-Eu compounds for these targets were calculated.

Bioassay-guided fractionation and in vitro and in silico biological activities of 2,4-di-tert-butylphenol isolated from Nocardiopsis sp. strain LC-8

In this study, an actinomycete strain was isolated from freshwater soil sediments to produce bioactive metabolite with a broad array of biological activities. Initially, preliminary antibacterial screening of isolate was performed by perpendicular streak method which showed the growth inhibition of all tested bacterial pathogens. Based on the culture characteristics, morphological identification, and 16S rRNA gene sequencing, the isolate was identified as Nocardiopsis sp. strain LC-8. Ethyl acetate extract of strain LC-8 showed potential antibacterial activity against tested bacterial pathogens with a maximum zone of inhibition of 16.98±0.57 mm against Staphylococcus aureus. After column chromatography, fraction 2 (F2) of the extract exhibited prominent growth inhibition activity against all tested bacterial and fungal pathogens. Antioxidant activity of F2 showed potent free radical scavenging activity with low IC50 values (DPPH - 278.15±0.35 μg/mL, ABTS - 367.55±1.13 μg/mL, and FRAP - 347.48±1.35 μg/mL). Total phenolic content of F2 was quantified as 362.44±1.25 mg gallic acid equivalent/gram extract. As per spectral analyses, the isolated compound from F2 was identified as 2,4-di-tert-butylphenol which further induced cytotoxic (IC50 value - 17.5±1.5 μg/mL) and apoptosis activity against MCF-7 cells. Molecular interaction studies of 2,4-di-tert-butylphenol with target proteins of pathogens and cancer cells displayed good docking score values. Finally, molecular dynamics simulation was performed to determine the stable structure of the protein-ligand system and effectiveness of 2,4-di-tert-butylphenol against the target protein. In conclusion, Nocardiopsis sp. strain LC-8 may act as a promising source for the production of 2,4-di-tert-butylphenol aiding diverse therapeutic roles.

Molecular docking of sterol derivatives in Tagetes erecta Linn. as an antiatherosclerotic agents through activation of PPARγ and LXRα receptors

Atherosclerosis is a condition characterized by inflammation in the arteries, which is linked with the accumulation of lipids and alterations in metabolism. Considering that atherosclerosis is the main factor causing death in the world, it is necessary to carry out immediate prevention and treatment to reduce the risk of developing clinical severity. The creation of foam cells, which originate from macrophages, is considered a key element in cardiovascular ailments, particularly in the advancement of atherosclerosis. Two types of the nuclear receptors known as Peroxisome proliferator-activated receptor γ (PPARγ) and liver X receptor α (LXRα), which serve as a primary regulator of cholesterol, intracellular lipid homeostasis and they are instrumental in the process of reverse cholesterol transport (RCT). Activation of these receptors could potentially decrease foam cell formation, consequently lowering the risk of atherogenesis and reducing cardiovascular disease risk. This research aims to determine sterol derivative compounds in Tagetes erecta Linn. which have the best interaction and potential as anti-atherosclerosis through peroxisome proliferator-activated receptor γ (PPARγ) and liver X receptor α (LXRα) activation. The analysis of this study is using docking molecular analysis. The parameters observed in this study were docking score, visualization results, absorption, distribution, metabolism, excretion profile, and toxicity value. The molecular docking outcomes indicate that β-sitosterol and 7β-hydroxysitosterol possess the most favorable binding energy values. They exhibit a positive pharmacokinetic profile, with the exception of gastrointestinal absorption and respiratory toxicity.

Investigation of the molecular structure of CHBP, biological activities and SARS-CoV-2 protein binding interaction by molecular and biomolecular spectroscopy approaches

The objective of this investigation is to learn more about the structural, electrical, spectroscopic, and physiochemical characteristics of biologically active cyano-4′-hydroxybiphenyl (CHBP). The title molecule’s optimized conformational analysis was computed using the DFT/B3LYP/6–311++G (d, p) level of theory. The observed wavenumbers were compared with theoretical FT-IR and FT-Raman spectra. 1H and 13C NMR experimental spectra in CDCl3 solution (solvent phase) were recorded and the chemical shift was calculated. NBO analysis was used to examine the transfer of charge as well as the intermolecular and intramolecular bonding of orbitals. The TD-DFT (time-dependent DFT) approach was used to estimate theoretical values for both the gas and solvent (ethanol) in the corresponding transitional research, which was conducted using UV–Vis’s spectra. Energy gap (Eg = 0.26764 eV) implies that the strong potential for charge transfer, and the stability of the CHBP compound. CHBP compound’s has bioactive nature, its drug-likeness and biological properties were evaluated. The predicted topological polar surface area of 44.02 \\AA2 for the molecule falls within the permissible range of < 140 \\AA2. Based on the docking results, the most stable docking score value is −6.84 kcal/mol. In that interaction, MET 165 affects both phenyl rings in a pi-sulphur fashion and a single bond hydrogen with protein moieties GLN 192. This suggests that the pi-alkyl in PRO 168 is a hydroxyl substitutional ring. Our findings demonstrate the CHBP compound is a good inhibitor against the SAR COVID-19 viral protein.

Design Synthesis and Spectral Characterization of Novel Morpholine ring fused with Substituted Pyrazoline Derivatives as Promising Anticancer, Antimicrobial Activity of in vitro and in silico studies

A search for new anticancer agents has prompted the design and synthesis of new novel morpholine ring fused with substituted pyrazoline derivatives MCP 1-4 as potent anticancer agents. MCP compounds were synthesized and the compounds structures were elucidated using elemental analysis and spectroscopic techniques like FT-IR, 1H NMR and 13C NMR. MCP derivatives binding affinities values were predicted by Auto Dock version, which shows the MCP derivatives as good anticancer 1OQA protein and antimicrobial properties, bacterial protein 1UAG and 5KEE with good binding affinity values from -6.2 to -6.5 kcal/mole and -7.6 to -8.9 kcal/ mole respectively. Among the four MCP compounds, the compounds MCP-1,3 and 4 have the similar binding interaction values of 6.5 kcal/mole. The MCP derivatives have good virus inhibition activity and these compounds are docked with SARS COVID 19 CORONA virus protein 6LU7 to have the docking score values -7.4 to 7-7.6 kcal/ mole. In silico ADME predictions were carried for the synthesized MCP 1-4 derivatives by online tool Swissadme. MCP derivatives have the good log p value of &lt;5. MCP derivatives were also evaluated by antimicrobial activity, the compound MCP-3 showed zone of inhibition values on all the sixteen bacterial cell lines. The compound MCP-3 was subjected to anticancer screening on MCF-7 cell line, the compound showed the good IC50 value.

Investigation of Newly Synthesized Fluorinated Isatin-Hydrazones by In Vitro Antiproliferative Activity, Molecular Docking, ADME Analysis, and e-Pharmacophore Modeling.

In this study, we investigated the in vitro antiproliferative activities and performed computational studies of newly synthesized fluorinated isatin-hydrazones. The chemical structures of the synthesized compounds were confirmed by FT-IR, 1D NMR (1H- and 13C NMR and APT), 2D NMR (HETCOR and HMBC), and elemental analysis. All compounds (1-15) were tested in human lung (A549) and liver (HepG2) cancer cell lines for 72 h. The compounds were screened against a healthy embryonic kidney cell line (HEK-293T) under the same conditions to determine their toxic effects. According to the results obtained, one of the compounds, in particular, compound 8 was effective at inhibiting the growth of cancerous cells, and its effects on both cancer cell lines were similar to IC50 values of 42.43 and 48.43 μM for A549 and HepG2, respectively. Compound 8, which was determined to be the best anticancer agent in vitro, was chosen to interact with the target via molecular docking. This selected ligand (compound 8) interacted with the targets 4HJO, 4ASD, 3POZ, and 7TZ7, and docked into the active sites. The docking score, Glide energy, and Glide emodel values were calculated and determined to be lower than those of the reference compound cisplatin. The pharmacokinetic properties, stability, and drug-likeness parameters of all designed compounds were estimated using SwissADME. Finally, the binding affinities of compound 8 for all four targets were calculated using the MM-GBSA method.

&lt;i&gt;In Silico&lt;/i&gt; Screening of a Phytochemical Naringin, Isolated from &lt;i&gt;Citrus decumana&lt;/i&gt; var. &lt;i&gt;paradisi&lt;/i&gt; Against the Genes of Polycystic Ovary Syndromenes of Polycystic Ovary Syndrome

Polycystic Ovary Syndrome (PCOS) is a complex hormonal and metabolic disorder. The overproduction of androgens is the primary feature of PCOS. The currently available pharmacological agents recommended for the treatment of PCOS are linked with several adverse effects. Therefore, herbal-based drugs with lesser side effects, have become a favourable trend among people. A flavonoid glycoside, naringin isolated from different fruit parts of Citrus decumana var. paradisi (Macfad.) H.H.A. Nicholls exhibits a wide range of therapeutic properties. In the traditional system of medicine, it is used to improve ovarian health. To set down scientific evidence, molecular docking analysis was performed to find out the binding affinity of compound naringin with the protein CYP 17-cytochrome P 450, attributing to hyperandrogenism due to its overexpression, leading to PCOS. The docking score values were compared with the standard drug metformin to interpret the effectiveness of flavonoid naringin in the treatment of PCOS.

Machine learning accelerates pharmacophore-based virtual screening of MAO inhibitors

Nowadays, an efficient and robust virtual screening procedure is crucial in the drug discovery process, especially when performed on large and chemically diverse databases. Virtual screening methods, like molecular docking and classic QSAR models, are limited in their ability to handle vast numbers of compounds and to learn from scarce data, respectively. In this study, we introduce a universal methodology that uses a machine learning-based approach to predict docking scores without the need for time-consuming molecular docking procedures. The developed protocol yielded 1000 times faster binding energy predictions than classical docking-based screening. The proposed predictive model learns from docking results, allowing users to choose their preferred docking software without relying on insufficient and incoherent experimental activity data. The methodology described employs multiple types of molecular fingerprints and descriptors to construct an ensemble model that further reduces prediction errors and is capable of delivering highly precise docking score values for monoamine oxidase ligands, enabling faster identification of promising compounds. An extensive pharmacophore-constrained screening of the ZINC database resulted in a selection of 24 compounds that were synthesized and evaluated for their biological activity. A preliminary screen discovered weak inhibitors of MAO-A with a percentage efficiency index close to a known drug at the lowest tested concentration. The approach presented here can be successfully applied to other biological targets as target-specific knowledge is not incorporated at the screening phase.

Purification, Molecular Docking and Cytotoxicity Evaluation of Bioactive Pentacyclic Polyhydroxylated Triterpenoids from Salvia urmiensis.

Triterpenoids, as one of the largest classes of naturally occurring secondary metabolites in higher plants, are of interest due to their high structural diversity and wide range of biological activities. In addition to several promising pharmacological activities such as antimicrobial, antiviral, antioxidant, anti-inflammatory and hepatoprotective effects, a large number of triterpenoids have revealed high potential for cancer therapy through their strong cytotoxicity on cancer cell lines and, also, low toxicity in normal cells. So, this study was aimed at discovering novel and potentially bioactive triterpenoids from the Salvia urmiensis species. For this, an ethyl acetate fraction of the acetone extract of the aerial parts of the plant was chromatographed to yield five novel polyhydroxylated triterpenoids (1: -5: ). Their structure was elucidated by extensive spectroscopic methods including 1D (1H, 13C, DEPT-Q) and 2D NMR (COSY, HSQC, HMBC, NOESY) experiments, as well as HRESIMS analysis. Cytotoxic activity of the purified compounds was also investigated by MTT assay against the MCF-7 cancer cell line. Furthermore, a molecular docking analysis was applied to evaluate the inhibition potential of the ligands against the nuclear factor kappa B (NF-κB) protein, which promotes tumor metastasis or affects gene expression in cancer disease. The 1β,11β,22α-trihydroxy-olean-12-ene-3-one (compound 4: ) indicated the best activity in both in vitro and in silico assays, with an IC50 value of 32 µM and a docking score value of - 3.976 kcal/mol, respectively.

Synthesis, Spectroscopic, Computational Structure Analysis, Molecular Docking, in vitro Antibacterial and in vivo Antipyretic Investigations of Transition Metal(II) Complexes

Unsymmetrical Schiff base hydrazone complexes of cobalt(II), nickel(II) and zinc(II) were synthesized from oxalic dihydrazide, salicylaldehyde and ethyl acetoacetate. The ligand and its metal(II) complexes were characterized by elemental analysis, UV-visible, FT-IR, molar conductivity. To determine the biological activity, in vivo antipyretic as well as in vitro antibacterial activities were conducted along with molecular docking simulation, HOMO-LUMO and MEP calculations. The findings from the experimental and molecular docking investigations demonstrated that the ligand and all the metal(II) complexes has an ability to interact with E. coli 24kDa domain protein (PDB: 1KZN). Furthermore, these interactions were accompanied by favourable docking score values, indicating potential therapeutic implications. The quantum parameters and geometric optimization of the ligand and complexes were performed using DFT simulations.

In-silico and in-vitro screening of Asiatic acid and Asiaticoside A against Cathepsin S enzyme

BackgroundAtherosclerosis is a form of cardiovascular disease that affects the endothelium of the blood vessel. Series of events are involved in the pathophysiology of this disease which includes the breaking down of the connective tissue elastin and collagen responsible for the tensile strength of the arterial wall by proteolytic enzyme. One of these enzymes called Cathepsin S (CatS) is upregulated in the progression of the disease and its inhibition has been proposed to be a promising pharmacological target to improve the prognosis of the disease condition. Asiatic acid and asiaticoside A are both pentacyclic triterpenoids isolated from Centella asiatica. Their use in treating various cardiovascular diseases has been reported.MethodsIn this study through in silico and in vitro methods, the pharmacokinetic properties, residue interaction, and inhibitory activities of these compounds were checked against the CatS enzyme. The SwissADME online package and the ToxTree 3.01 version of the offline software were used to determine the physicochemical properties of the compounds.ResultAsiatic acid reported no violation of the Lipinski rule while asiaticoside A violated the rule with regards to its molecular structure and size. The molecular docking was done using Molecular Operating Environment (MOE) and the S-score of − 7.25988, − 7.08466, and − 4.147913 Kcal/mol were recorded for LY300328, asiaticoside A, and asiatic acid respectively. Asiaticoside A has a docking score value (− 7.08466Kcal/mol) close to the co-crystallize compound. Apart from the close docking score, the amino acid residue glycine69 and asparagine163 both interact with the co-crystallized compound and asiaticoside A. The in vitro result clearly shows the inhibitory effect of asiaticoside and asiatic acid. Asiaticoside A has an inhibitory value of about 40% and asiatic acid has an inhibitory value of about 20%.ConclusionThis clearly shows that asiaticoside will be a better drug candidate than asiatic acid in inhibiting the CatS enzyme for the purpose of improving the outcome of atherosclerosis. However, certain modifications need to be made to the structural make-up of asiaticoside A to improve its pharmacokinetics properties.

Anti-Cancer Potential of Phytocompounds from Ziziphus jujuba against Lung Cancer Target Proteins: An In Silico Validation

Ziziphus jujuba plant belongs to Rhamnaceous family and grows mainly in Europe, southern and eastern Asia, and Australia. Recent phytochemical investigation of plants provided some information on their biological effects, such as the hepatoprotective, immunostimulating, anti-obesity, anti-inflammatory, and anti-cancer properties. The current study investigated 34 phytocompounds from Z. jujuba and three anti-cancer drugs against three lung cancer target proteins. Drug likeliness screening revealed that two compounds dodecanoic acid and 7,9-di-tert-butyl-1-oxaspiro[4,5]deca-6,9-diene-2,8-dione possess zero violation, and compound azelaic acid possesses single violation against five drug rules. Molecular docking study reveals that 34 phytocompounds from Z. jujuba and three anti-cancer drugs showed docking score values in the range of −3.9 to −10.2 kcal/mol and −7.2 to −9.0 kcal/mol against three significant lung cancer target proteins. Furthermore, in silico screening top scored three phytocompounds campesterol, stigmast-5-en-3-ol, 7,9-di-tert-butyl-1-oxaspiro[4,5]deca-6,9-diene-2,8-dione and three anti-cancer drugs etoposide, paclitaxel, and doxorubicin utilized. Pharmacokinetic profile of three phytocompounds from Z. jujuba showed excellent absorption, distribution, metabolism, excretion, and toxicity profile than standard drugs. Furthermore, bioactivity and density functional theory analysis showed that phytocompounds from Z. jujuba possess better bioactivity scores and molecular electrostatic potentials than standard drugs. Molecular dynamics simulation results revealed that campesterol with CDK2 (PDB ID 1GII) and MDM2/P53 (4HFZ) target proteins possess better simulation trajectories and binding affinity than standard drugs. Further clinical trials of compounds (campesterol, stigmast-5-en-3-ol, 7,9-di-tert-butyl-1-oxaspiro[4,5]deca-6,9-diene-2,8-dione) are needed to check clinical pertinence toward lung cancer target proteins to commercialize these novel drug molecule in the drug industry.

Synthesis of phenylthiourea-based pyrazole, thiazole and/or pyran compounds: molecular modeling and biological activity

The significant biological activity of phenylthiourea derivatives prompted the synthesis of a new phenylthiourea-based heterocyclic ring systems (pyrazole, thiazole, and pyran), and their chemical structures were elucidated by spectral data. The DFT/B3LYP methodology was applied to explore the configuration and energetic features of the FMO’s of the compounds. The derivatives exhibited comparable energy gap, ranging from 2.13 to 2.56 eV, and were arranged in the following order: 5 < 8 < 7 < 6 < 4b < 4a. The antitumor activity of the new phenylthiourea-based derivatives was investigated against diverse cell lines, such as HepG2, HCT-116, MCF-7, PC3, and WI38, using Doxorubicin as a reference drug. The hybrids 5, 6, and 8 revealed strong cytotoxic against HCT-116 (IC50 = 2.29 ± 0.46-9.71 ± 0.34 µM). Furthermore, the molecular docking studies of the compounds indicated that the hybrids 5, 6 and 8 exhibited the greatest docking score values, in accordance to the antitumor activity.

Potentiality of Organosulfur Compounds Against SARS-CoV-2-Coinfected Bacteria Streptococcus pyogenes and S pneumoniae: A Cross-Platform Analysis from Computational Chemistry

Objective SARS-CoV-2 coinfection with Streptococcus pyogenes and S pneumoniae increases disease severity, thus deserving more in-depth understanding. Methods The potential of garlic extract against the bacteria has been theoretically examined and extended to synergic predictions on SARS-CoV-2 Delta and Omicron variants. Results Gas chromatography–mass spectrometry characterized five main components in the extract: benzeneacetaldehyde (A1; 5.65%), diallyl disulfide (A2; 19.27%), 1-allyl-3-methyltrisulfane (A3; 21.30%), methyl salicylate (A4; 7.49%), and diallyl trisulfide (A5; 39.26%). Bioassay-based inhibition zones were 8 ± 2 mm, and MIC values 64 mg·mL−1 ( S pneumoniae) and 128 mg·mL−1 ( S pyogenes). Density functional theory suggested the organosulfur components as the most promising inhibitors with electrophilic sites at their sulfur atoms. Molecular docking simulation agreed with their potential against S pneumoniae/ S pyogenes luxS proteins and Delta/Omicron SARS-CoV-2 spike proteins, given by all docking score values being &lt;−13 kcal·mol−1. QSARIS and ADMET predicted their bio- and pharma-favored properties. Conclusion The consistency of a variety of computational outputs justifies the dietary–supplemental potential of garlic essential oil based on its organosulfur ingredients.

Evaluating the ability of some natural phenolic acids to target the main protease and AAK1 in SARS COV-2

Researchers are constantly searching for drugs to combat the coronavirus pandemic caused by SARS-CoV-2, which has lasted for over two years. Natural compounds such as phenolic acids are being tested against Mpro and AAK1, which are key players in the SARS-CoV-2 life cycle. This research work aims to study the ability of a panel of natural phenolic acids to inhibit the virus's multiplication directly through Mpro and indirectly by affecting the adaptor-associated protein kinase-1 (AAK1). Pharmacophore mapping, molecular docking, and dynamic studies were conducted over 50 ns and 100 ns on a panel of 39 natural phenolic acids. Rosmarinic acid (16) on the Mpro receptor (− 16.33 kcal/mol) and tannic acid (17) on the AAK1 receptor (− 17.15 kcal/mol) exhibited the best docking energy against both receptors. These favourable docking score values were found to be superior to those of the co-crystallized ligands. Preclinical and clinical research is required before using them simultaneously to halt the COVID-19 life cycle in a synergistic manner.

Assessment of antioxidant and DPPH free radical scavenging activity of 1,2-dithiole-3-thione derivatives by using cyclic voltammetry, spectroscopic, and molecular docking studies

The antioxidant and the DPPH free radical scavenging activity of 4-phenyl-3H-1,2-dithiole-3-thione (DT1), 5-(4-fluorophenyl)−3H-1,2-dithiole-3-thione (DT2), 5-(4-phenyl-3-thioxo-3H-1,2dithiol-5-yl)-benzo[d]oxazole-2(3H)thione (DT3) and 4-methyl-5-((phenylamino)methyl)−3H-1,2-dithiole-3-thione (DT4) was investigated using cyclic voltammetry (CV) and electronic spectroscopy (ES) assays. The diminution in anodic peak current density of an acetonitrile solution of DPPH in the absence and presence of gradually increasing amounts of 1,2-dithiole-3-thione derivatives (DT) was successfully exploited for measuring the antioxidant activity and the DPPH free radical scavenging activity. The EC50 values obtained from the CV and ES experiments suggested that all compounds had potential DPPH radical scavenging ability with the derivative DT3 possessing the highest potency of 21.5 ± 1.30 from CV and 20.6 ± 1.05 from ES. A molecular docking simulation indicated that all DT derivatives interacted with amino acid residues of glutathione reductase via hydrogen bonding and hydrophobic interactions. Based on the inhibitory concentration and docking score values, compound DT4 was the second inactive compound against the glutathione reductase enzyme having values equal to 41.4 µM and a docking score of −25.6 kJ/mol respectively. Toxicity perdition studies revealed that compounds DT1 and DT2 were non-toxic.

In silico Molecular Modelling and Docking Studies on Kinase Inhibitors as Potential Anti-Cancer Target in HER2-associated Breast Cancer

Abstract: Breast cancer is one of the most frequent invasive malignancies in women globally and the leading cause of mortality. The HER2 target is an important therapeutic option for treating breast cancer. In the present study, efforts have been made to virtually screen the natural kinase inhibitors through molecular docking. A total of 800 HER2 protein inhibitor compounds were selected to screen out the potential inhibitors of the HER2 protein. The docking study demonstrated that these HER2 protein inhibitors confirm the strong binding interaction with HER2 protein based on the docking score, indicating that kinase inhibitors can play a major role in preventing breast cancer. Among all the inhibitors, the flavanone compound named 6-C-(3-Hydroxyisopentyl) eriodictyol, IUPAC: 2-(3, 4- dihydroxyphenyl)-5, 7-dihydroxy-6-(3-hydroxy-3-methylbutyl)- 2, 3-dihydrochromen-4-one observed to have the maximum docking score value of (-8.717), indicating the highest binding affinity with HER2 protein which might serve as the promising compound for the development of a new class of drug to combat breast cancer.

Binding mechanism of anacardic acid, carnosol and garcinol with PCAF: A comprehensive study using molecular docking and molecular dynamics simulations and binding free energy analysis.

The p300/CBP associated factor bromodomain (PCAF Brd) is emerged as one of the promising target proteins for different types of cancers. PCAF is one among the histone acetyltransferase enzymes which involved in the regulation of transcriptase process by modifying the chromatin structure. Anacardic acid, carnosol, garcinol are the experimentally reported inhibitors of PCAF Brd; however, their detailed binding mechanism these inhibitors are not yet known. The intermolecular interaction, binding energy, and the stability of these inhibitors with the active site of PCAF Brd are playing the key role in the binding of these inhibitors with PCAF. The in silico study incorporates the molecular docking and dynamics simulations; these molecular level simulations allow to understand the binding mechanism. In the present study, the induced fit molecular docking and molecular dynamics of anacardic acid, carnosol and garcinol molecules against the PCAF Brd have been performed. The docking score values of these molecules are -5.112 (anacardic acid), -5.141 (carnosol), -5.199 (garcinol) and -3.641 (L45) kcal/mol, respectively. Further, the molecular dynamics simulation was carried out for these docked complexes to understand their conformational their stability and binding energy from the roots means square deviation (RMSD) and root means square of fluctuation (RMSF), and molecular mechanics with the generalized born and surface area solvation (MM/GBSA) binding free energy calculations. The intermolecular interactions and binding free energy values confirm that garcinol forms key interactions and has high binding affinity towards PCAF Brd on compare with the other two inhibitors. Therefore, garcinol may be considered as a potential inhibitor of PCAF Brd.

Antioxidant enzyme activities, molecular docking studies, MM-GBSA, and molecular dynamic of chlorpyrifos in freshwater fish Capoeta umbla

Chlorpyrifos (CPF), which was started to be used in 1965, is a broad spectrum organophosphate insecticide that is used more and more day by day. Commonly used to control pests in farmland and homes, CPF is more toxic to fish than organochlorine compounds. CPF poses a serious threat to the health of humans and aquatic organisms. This paper studies the relationship between CPF exposure and antioxidant enzyme activities in gill, kidney and liver tissues of Capoeta umbla. Different time intervals (12, 24, 48, 72, and 96 h) and CPF doses (55 and 110 µg L−1) were used in the study. Spectrophotometrical measures were taken in all tissues for antioxidant enzyme activities and malondialdehyde (MDA) levels, as indices of the lipid peroxidation (LPO). A positive relationship between CPF and MDA levels was found in the study at a statistically significant level (p < 0.05). The study also found a negative relationship between CPF levels and catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) activity. Independent variables in the study can act as biomarkers of CPF exposure. The study recommends employing proper ecotoxicological risk evaluations in cases of CPF usage as a pesticide. The activities of the studied molecules against various proteins that are crystal structure of human peroxiredoxin 5 (PDB ID: 1HD2) has docking score value is −2.67, crystal structure of Bovine Xanthine Oxidase (PDB ID: 3NRZ) has docking score value is −3.76, and crystal structure of antibacterial FabH (PDB ID: 4Z8D) has docking score value is −3.16, were compared. Molecular dynamic (MD) calculations were made in 100 ns. MM/GBSA methods are calculated binding free energy. Afterwards, ADME/T analysis was performed to examine the some properties of the molecules. Communicated by Ramaswamy H. Sarma

Chitosan Schiff base electrospun fabrication and molecular docking assessment for nonleaching antibacterial nanocomposite production

In this work, new chitosan derivative nanofibers that exhibit antibacterial properties were successfully fabricated. The two CS Schiff base derivatives (CS-APC and CS-2APC) were prepared by incorporating 4-amino antipyrine moiety in two different ratios, followed by a reductive amination to obtain the corresponding derivatives CS-APCR and CS-2APCR. Spectral analyses were used to confirm the chemical structure. The molecular docking evaluation of CS-APC, CS-APCR, and CS was conducted on DNA topoisomerase IV, thymidylate kinase and SARS-CoV-2 main protease (3CLpro) active sites. CS-APCR showed a well-fitting into the three enzyme active sites with docking score values of − 32.76, − 35.43 and − 30.12 kcal/mol, respectively. The nanocomposites of CS derivatives were obtained by electrospinning the blends of CS-2APC and CS-2APCR with polyvinyl pyrrolidone (PVP) at 20 kV. The morphology of the nanofibers was investigated by scanning electron microscopy (SEM). It was found that fiber diameters were significantly decreased when CS-2APC and CS-2APCR were incorporated into pure PVP to reach 206–296 nm and 146–170 nm, respectively, compared to 224–332 nm for pure PVP. The derivatives of CS and their nanofibers with PVP were found to have antibacterial activities against two strains of Staphylococcus aureus and Escherichia coli. Data revealed that CS-2APC nanofibers showed antibacterial activity to the two strains of E. coli less than CS-2APCR nanofibers.