Docking Simulations Research Articles

Identifying Luteolin as a Potential Drug for Treating Lung Adenocarcinoma with COVID-19 Affection based on Integration Analysis of Pharmacology and Transcriptome.

Lung adenocarcinoma (LUAD) is a major type of lung cancer worldwide, and under the pandemic coronavirus disease 2019 (COVID-19), its cancer burden is enlarged. This study aimed to explore potential drug targets and potential drugs for developing effective treatments for patients with both lung cancer and COVID-19. The interaction network of molecule compounds-target genes was constructed based on Traditional Chinese Medicines (TCMs) and gene expression data from public databases. The potential effectiveness of drugs was analyzed by molecular docking and molecular dynamics simulation. Western blot, transfection assay, Immunohistochemistry (IHC) staining, and flow cytometry were performed to investigate the function of HSP90AA1 in LUAD cells. Eight target genes (GSK3B, HMOX1, HSP90AA1, ICAM1, MAPK1, PLAU, RELA and TNFSF15.) were identified, and two of them (HSP90AA1 and RELA) were significantly associated with LUAD prognosis. Luteolin was discovered to bind with HSP90AA1. Moreover, in vitro cell experiments demonstrated that HSP90AA1 had higher expression in A549 cells, promoted cell viability and suppressed apoptosis in A549 cells and H1299 cells. HSP90AA1 was a target gene for further designing effective drugs for LUAD patients. Luteolin was a potential drug for treating patients with both LUAD and COVID-19.

Insights into lipid-modified recognition of Apolipoprotein E3 to extra-cellular domain of TREM2 associated with Alzheimer’s disease

E3 genotype of apolipoprotein E (ApoE) and triggering receptor expressed on myeloid cells 2 (TREM2) are critical genetic risk factors for late-onset Alzheimer’s diseases (AD) that influences the formation of plaques and neurofibrillary tangles associated with AD pathogenesis. In addition, variation in genetic association of ApoE and TREM2 in presence of lipids have been advocated to potentially regulate different aspects of AD pathology by facilitating the clearance of amyloid beta (Aβ) from brain. However, the proteinopathy and functional mechanism underlying their molecular interaction in presence of lipid remains poorly understood. Herein, to shed inherent insights into the mode of ApoE3-TREM2 interaction in both lipid and aqueous medium, we have used a combination of different state-of-the-art computational tools including knowledge-based protein–protein docking and molecular dynamics (MD) simulations. Remarkably, we find the direct involvement of regulatory complementarity-determining region-2 (CDR2) loop of TREM2 in interaction with the major hinge region and helix H4 of ApoE3. We further anticipate that ApoE3 attains distinct conformational states and forms an open and extended cavity-like structure in ApoE3-TREM2 complex in presence of lipids. Our data also exhibits reduced hydrophobicity in the ApoE3 binding interface of TREM2, which sets a baseline for reduced binding affinity towards ApoE3. Therefore, we hypothesize that this decline in hydrophobic index might have resulted due to structural variations in the H4 helix and major hinge region leading to altered TREM2 conformation in presence of lipids. Altogether, our findings demonstrate the effect of phospholipids on the structural dynamics and conformation of ApoE3, which contributes to our understanding of how APOE and TREM2 influences the development of AD. However, further experimental studies are necessary to validate and explore our findings which will open up new avenues towards development of novel therapeutic strategies for AD.

A study on loading multiple epitopes with a single peptide.

Epitopes, the basic functional units of antigens, hold great significance in the field of immunology. However, the structure and composition of epitopes and their interactions with antibodies remain unclear, which limits in-depth studies on epitopes and the development of subunit vaccines. In a previous study on the localization of anti-influenza HA monoclonal antibodies (mAbs), three strains with different characteristics reacted with the same peptide. In this study, by conventional immunological assays, computer homology modeling, and molecular docking simulations, we found that (1) the peptide could bind to three strains of mAbs with different reaction characteristics utilizing different combinations of immunodominant groups. (2) By computer molecular docking and simulation methods, the immunodominant groups on the two peptides could be combined into a multi-epitope peptide bound to six strains of mAbs. We established a method for multi-epitope peptide recombination from these immunodominant groups. (3) The immune effect of the recombinant multi-epitope peptide was better than that of a single peptide. Our findings facilitate the understanding of the composition of antigen epitopes and provide a theoretical and experimental basis for developing polyvalent vaccines and understanding immune responses at the molecular level.

Targeting TLR4 and regulating the Keap1/Nrf2 pathway with andrographolide to suppress inflammation and ferroptosis in LPS-induced acute lung injury

Acute lung injury (ALI) is a severe inflammatory condition with a high mortality rate, often precipitated by sepsis. The pathophysiology of ALI involves complex mechanisms, including inflammation, oxidative stress, and ferroptosis, a novel form of regulated cell death. This study explores the therapeutic potential of andrographolide (AG), a bioactive compound derived from Andrographis, in mitigating Lipopolysaccharide (LPS)-induced inflammation and ferroptosis. Our research employed in vitro experiments with RAW264.7 macrophage cells and in vivo studies using a murine model of LPS-induced ALI. The results indicate that AG significantly suppresses the production of pro-inflammatory cytokines and inhibits ferroptosis in LPS-stimulated RAW264.7 cells. In vivo, AG treatment markedly reduces lung edema, decreases inflammatory cell infiltration, and mitigates ferroptosis in lung tissues of LPS-induced ALI mice. These protective effects are mediated via the modulation of the Toll-like receptor 4 (TLR4)/Kelch-like ECH-associated protein 1(Keap1)/Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Molecular docking simulations identified the binding sites of AG on the TLR4 protein (Kd value: -33.5 kcal·mol-1), and these interactions were further corroborated by Cellular Thermal Shift Assay (CETSA) and SPR assays. Collectively, our findings demonstrate that AG exerts potent anti-inflammatory and anti-ferroptosis effects in LPS-induced ALI by targeting TLR4 and modulating the Keap1/Nrf2 pathway. This study underscores AG's potential as a therapeutic agent for ALI and provides new insights into its underlying mechanisms of action.

Enantioselective Separation and Pharmacokinetics of a Chiral 1,4-Dihydropyrimidine Derivative in Rats: A Combined Chromatography and Docking Approach.

Chirality in 1,4-Dihydropyrimidines influences their pharmacological properties and synthetic strategies. Enantiomers of chiral drugs often exhibit different pharmacokinetic profiles. Therefore, separating and studying individual enantiomers is crucial to optimize drug efficacy and safety. Enantiomeric separation of ±4-(4-chlorophenyl)-6-methyl-2-oxo-N-(O-toyl)-1,2,3,4-tetrahydropyrimidine-5-carboxamide (DP-1), which is a 1,4-Dihydropyrimidine derivative is achieved on CHIRALCEL® OD-H column (particle size: 5 μm, inner diameter: 4.6 mm, length:150 mm), following by investigating the kinetic properties of (R) and (S) enantiomers. The separation was achieved with a mobile phase composed of 70% (v/v) isopropyl alcohol and 30% (v/v) n-hexane. For the bioanalytical study, acetonitrile was used to precipitate the rat plasma samples and validated the method according to USFDA guidelines. The validated bioanalytical method was then successfully applied to determine the pharmacokinetic parameters of the drug in biological samples. Molecular modeling techniques, specifically docking simulations, were employed to predict the elution order of DP-1 enantiomers. The docking results revealed moderate binding interactions between the enantiomers and the chiral stationary phase (CSP), which aligns with the theoretical expectation that stronger interactions lead to longer retention times on the column.

Synthesis, characterization, antimicrobial, anticancer and the theoretical calculation of a novel N, O-multidentate chelating ligand and its Cu(II) and Fe(III) complexes

A new group of Cu(II) and Fe(III) complexes has been produced utilizing the ligand (Z)-N′-(1-(thiophen-2-yl)ethylidene)-2-(p-tolylamino)acetohydrazide (H2L). The chemical structure of new compounds has been established using FT-IR, 1H NMR, electronic spectra, powder X-ray diffraction, and thermal behavior. The Gaussian 09 program used the Density Functional Theory (DFT) approach to optimize the geometry of all synthesized compounds to acquire the best possible structures and significant parameters. The examination of biological aspects included the study of microbial and breast cancer cell lines. It was found that both the ligand and the complexes exhibited strong antibacterial activity against the studied bacterial species. The complexes worked as strong antifungal agents filamentous fungi like Candida albicans. The H2L ligand and its Cu(II) complexes (M1 and M2) were more effective against Candida albicans than Fe(III) complex, which showed no activity against Aspergillus niger. Both mononuclear and binuclear copper (II) complexes expanded their antifungal capabilities to target Aspergillus niger, surpassing the effectiveness of the standard drug. Amphotericin was used as a reference. Following testing against the MCF-7 breast cancer cell line, the reactivity of all compounds was investigated. All complexes showed an intriguingly powerful antiproliferative potential. The compounds’ activities were organized like this: Cu(II) Complexes (M2, M1) > Fe(III) Complex (M3) > H2L Ligand. Molecular docking simulation identified the active amino acids relevant to microbial and breast cancer studies.

Structural investigation, DNA/Mpox/COVID-19 molecular docking, and biological assays of two novel Co(II) and Cu(II) complexes derived from tri- and bi-dentate pyridyl-functionalized phosphoramide ligand [Ph]P(O)[NH-2Py]2

Phosphoramides have recently gained significant attention in medical and pharmaceutical research due to their diverse biological applications, including anticancer and antiviral drugs. Here, novel phosphoramide complexes [Co(II){(O)P[NH-2Py]2[Ph]}2][CoCl4] (1) and [Cu(II){(O)P[O][NH-2Py][Ph]}2{OH2}].2H2O (2) derived from [Ph]P(O)[NH-2Py]2 were synthesized and characterized by FT-IR, CHN elemental analysis and single crystal X-ray diffraction. In these discrete chelate complexes the phosphoramide [Ph]P(O)[NH-2Py]2 moiety acts as a flexible tridentate O,N,N-donor ligand for 1 or bidentate N,O-donor ligand for 2. The metal cation has a hexa-coordinate M(N)4(O)2 environment adopting a distorted octahedral geometry for 1 and a penta-coordinate M(N)2(O)3 environment with a distorted square pyramidal geometry for 2. The supramolecular assemblies have 1D linear arrangements along the [201] axis formed via NH…Cl hydrogen bond interactions for 1 and 2D arrangements parallel to the ab plane formed via classical NH…O and OH…O hydrogen bonds for 2. The in vitro anticancer activity of 1 and 2 was assessed against MDA-MB-231 breast cancer cell line showing a good inhibitory effect for both compounds, especially for the Cu(II) complex 2 with a IC50 of 29 ± 2.1 nmolar. Antioxidant and anti-hemolytic potential of 1 and 2 was experimentally evaluated using the DPPH technique showing suitable performance for both compounds. The binding capacity of 1 and 2 to DNA was investigated using molecular docking simulations showing a good correlation with the experimental in vitro results. The results reveal mixed modes of interactions between the compounds with the DNA receptor confirming a suitable DNA-binding ability for both 1 and 2. In silico molecular docking technique was also employed to provide a detailed prediction of the binding affinity of the studied compounds for SARS-CoV-2 (−6.5 kcal/mol) and Monkeypox (−8.4 kcal/mol)) which competes with current effective drugs.

Synthesis of new 1,4-benzodioxin derivatives containing thiazolidin-4-one skeleton, molecular modelling and docking as antibacterial agents

In this study, we synthesized a variety of 1,4-benzodioxin derivatives containing the thiazolidin-4-one skeleton and evaluated their antimicrobial properties. Several of the newly synthesized compounds exhibited potent inhibitory effects against the Gram-negative bacteria Escherichia coli. By conducting molecular docking simulations and molecular dynamics with the fatty acid synthesis enzyme FabH, we unveiled the potential antimicrobial activity of these compounds, suggesting they interfered with fatty acid biosynthesis pathways. Additionally, we optimized compound 3b and assessed its ability to disrupt biofilms using live/dead cell staining techniques. The results highlighted significant biofilm disruption, enhancing the compounds' antimicrobial efficacy. These findings provided valuable insights for the development of novel antimicrobial agents and presented a promising avenue for addressing antimicrobial resistance through innovative therapeutic approaches.

Insights into Antibacterial Design: Computational Modeling of Eugenol Derivatives Targeting DNA Gyrase

The rise of antibiotic resistance underscores the urgent need for novel antibacterial agents. DNA gyrase, an essential enzyme involved in bacterial DNA replication, is a promising target for antibacterial therapy. Computational approaches offer a cost-effective means to design and screen potential inhibitors, such as eugenol derivatives. This study aims to computationally design eugenol derivatives as potential antibacterial agents targeting DNA gyrase, assess their binding affinities, evaluate physicochemical properties, and toxicity, and select lead compounds for further investigation. Molecular docking simulations were conducted to investigate the binding affinities of eugenol derivatives and controls to DNA gyrase. Physicochemical properties and toxicity assessments of eugenol were evaluated. Lead compounds were selected based on drug likeness, toxicity, and binding affinity. Molecular docking studies revealed varying binding affinities of eugenol derivatives to DNA gyrase, with lead compounds exhibiting superior affinity compared to eugenol. Physicochemical properties indicated moderate lipophilicity and low aqueous solubility for eugenol. Toxicity assessment revealed mutagenicity and tumorigenicity. De novo compound synthesis generated 244 novel compounds, with 44 selected based on drug-likeness, toxicity, and binding affinity as lead candidates. These findings provide valuable insights for the development of novel antibacterial agents targeting DNA gyrase, with implications for combating antibiotic resistance.

Exploration of pyridine-thiazolidin-4-one: Synthesis, DFT study, UV–Vis/ fluorescence spectroscopy analysis, antibacterial evaluation and molecular docking

The synthesis of the objective pyridine-thiazolidin-4-one (DCPI-MBT) was involved via the Knoevenagel reaction between 2-((3,5-dichloropyridinyl)imino)thiazolidinone derivative 1 and 4-methylbenzaldehyde 2 over refluxing in acetic acid and sodium acetate. The confirmed structure of this hybrid was elucidated through detailed spectral analyses. A comparison was made between the density functional theory (DFT) configurations of the frontier molecular orbitals in both the gas and solvated ground state (So) and the solvated excited state (S1). UV–Visible and fluorescence spectra of the thiazolidin-4-one derivative were obtained in DMSO, displaying a significant Stokes’ shift (Δν¯= 3136.81 cm−1). The synthesized DCPI-MBT was established to see how well they killed different kinds of pathogenic microbes, such as bacteria, viruses, and fungi. These results demonstrate that the synthesized DCPI-MBT has a broad-spectrum antibacterial capability that is on par with or even superior to conventional treatments in certain instances. Moreover, molecular docking simulation was used to evaluate the bindings of the synthesized DCPI-MBT with a target protein (PDB: 1kzn). The binding energies, RMSD values, kinds of interactions with amino acid residues, and interaction distances of the hybrids were determined based on their substituent changes. This study analyzed the pharmacokinetic profiles of newly DCPI-MBT, using SwissADME predictions to focus on their potential as therapeutic agents. The DCPI-MBT has the promising pharmacokinetic profile for future development as a therapeutic drug, with optimum solubility, bioavailability, and a favorable interaction profile with biological targets.

Computational and in vitro analyses of the antibacterial effect of the ethanolic extract of Pluchea indica L. leaves.

The most common gram-negative, Escherichia coli, and gram-positive bacteria, Bacillus spp., have evolved different mechanisms that have caused the emergence of multi-drug resistance. As a result, drugs that block the bacterial growth cycle are needed. Here, in silico and in vitro studies were performed to assess compounds in the Pluchea indica leaf extract, a medicinal plant, that can inhibit bacterial proteins. Briefly, P. indica leaves were extracted using ethanol. The crude extract was then subjected to gas chromatography-mass spectrometry for metabolite screening. Molecular docking simulations with rhomboid protease (Rpro) (Protein data bank ID number: 3ZMI from E. coli and filamenting temperature-sensitive mutant Z (FtsZ) protein data bank ID number: 2VAM from Bacillus subtilis were performed. Moreover, the well diffusion method was used to confirm the antibacterial activity of P. indica leaf extract. A total of 10 compounds were identified in the P. indica extract and used for computational analysis. Based on drug-likeness prediction, P. indica compounds may be drug-like molecules. Binding affinity tests indicated that 10,10-Dimethyl-2,6-dimethylenebicyclo(7.2.0)undecan-5.β.-ol and 11,11-Dimethyl-4,8-dimethylenebicyclo(7.2.0)undecan-3-ol had the most negative values. Accordingly, these compounds may be potential ligands that bind to bacterial proteins. The root mean square fluctuation values was <2 Å, indicating stable fluctuation binding for the ligand-protein complex. According to in vitro antibacterial assays, a high concentration (50%) of the P. indica extract markedly inhibited E. coli and B. subtilis, with inhibitory zone diameters of 31.86±1.63 and 21.09±0.09 mm, respectively. Overall, the compounds in the P. indica leaf extract were identified as functional inhibitors of E. coli and B. subtilis proteins via in silico analysis. This may facilitate development of antibacterial agents.

Identification of Potent CHK2 Inhibitors‐Modulators for Therapeutic Application in Cancer: A Machine Learning Integrated Fragment‐Based Drug Design Approach

AbstractThe CHK2 protein regulates the cell division cycle and responds to DNA damage. Additionally, it facilitates the repair of DNA damage and maintains the integrity of its biological processes. Dysregulation of the CHK2 protein is associated with a predisposition to harmful diseases. The current research protocol was designed to identify novel hit molecules as CHK2 inhibitors and disrupt the normal biological function of the CHK2 protein via a fragment‐based drug discovery approach. The protocol involved generating fragments using the MacFrag tool, followed by a chemical similarity search utilizing RDKit to identify fragment molecules analogous to previously established CHK2 inhibitor scaffolds. The bioactive molecules were constructed using the Fragmenstein tool, followed by molecular docking simulations to investigate their binding affinity. In addition, pharmacokinetic properties were analyzed, and a molecular dynamics simulation study was conducted to assess the stability of selected compounds with CHK2 protein. Finally, five novel compounds were identified as excellent CHK2 inhibitors through the FBDD and show good binding interactions at active sites of CHK2 with beneficial ADMET properties. This research work presents novel CHK2 inhibitor molecules that have the potential to be utilized in drug discovery, serving as key leads for future advancements in healthcare industries and sectors.

Synthesis of new pyrazoles, thiadiazoles, and trizolotriazines compounds that act as an antibacterial agents using C-ethoxycarbonylhydrazonoyl chloride precursor: Molecular docking simulation and in silico ADMET prediction studies

Treatment of C-ethoxycarbonylhydrazonoyl chloride with active methylene-containing compounds such as dibenzoylmethane or malononitrile in sodium ethoxide solution yielded in each case pyrazole derivatives. The latter pyrazoles were used as a useful precursors in the synthesis of new heterocyclic compounds like pyrazoles and 1,3,4-thiadizaoles upon reaction with hydrazonoyl halides. Also, the reaction of C-ethoxycarbonylhydrazonoyl chloride with the approperiate triazinethiones in chloroform in the presence of catalytic amount of triethylamine at reflux yielded the corresponding triazolotriazines. The structures of the newly synthesized compounds were confirmed based on elemental analyses and spectral data. The antibacterial activities were studied against two gram-positive and two gram-negative bacteria, the results represented that compound 26a showed antibacterial activity against Salmonella (22 mm) and E. coli (6 mm), as well as compound 26b against Salmonella (5 mm) and Staphylococcus aureus (10 mm) while the rest compounds showed no antibacterial activities. The molecular docking simulation was investigated for the most active compounds 26a and 26b. The results confirm that compounds 26a and 26b are promising candidates for potential inhibitors of DNA gryA (P37411) of Salmonella and Transpeptidases of Staphylococcus aureus.

Revealing protein aggregation behaviour and dispersion properties induced by molecular interactions between sucrose esters and myofibrillar protein in an aqueous phase system

The effects of sucrose esters (SE) with varying hydrophilic-lipophilic balance (HLB) values (SE 11, 13, 15) and different concentrations (0.01, 0.1, 1.0 mM) on the dispersion properties and structure of myofibrillar proteins (MPs) in the aqueous phase were investigated. The results demonstrated that the SE 11 and SE 13 reduced the particle size and enhanced the distribution uniformity of the MPs. All of the SE exhibited a slight reduction in the ζ-potential absolute values of the MPs. Meanwhile, the SE 11 significantly reduced the turbidity of the MPs, especially in the 0.1 mM group. Macroscopic and microscopic images showed that the optimum dispersion state was in the SE 11–0.1 group. Furthermore, the interactions between SE and MPs exerted a significant impact on the proteins structure. The SE 13 and SE 15 caused significant changes, which presented concentration correlation, in the tertiary and secondary spatial structures of the MPs. Nevertheless, slight structural changes were observed in MPs with different SE11 concentrations. The SE did not alter the molecular weight of the MPs, i.e. it did not induce irreversible aggregation, nor degradation of the proteins. These results were verified by the surface hydrophobicity, UV–Vis spectroscopy, intrinsic fluorescence, circular dichroism, and SDS-PAGE. Molecular docking simulation showed that hydrophobic interactions and hydrogen bonds were the main interaction force between SE 11 and MPs. Therefore, our findings provided meaningful insights into the dispersion state of the MPs aqueous containing SEs and contributed to the practical application of non-ionic surfactants in meat protein processing.

In Silico ADME And Molecular Docking Studies of New Thiazolyl-bipyrazole, Pyrazolopyridine and Pyrano[2,3-d]pyrazolopyridine Derivatives as Antibacterial Agents

: In this study, a series of novel pyrazole-based compounds were synthesized starting from the precursor ethyl 3-(4-amino-1-phenyl-3-((4-sulfamoylphenyl)carbamoyl)-1Hpyrazol- 5-yl)-3-oxopropanoate (2). Various synthetic routes were used to obtain pyrazolylpyrazolone 3, tricyclic dipyrazolopyridine 4a-c, thiazolyl-bipyrazoles 5 &amp; 6, pyrazolo[4,3- b]pyridines 7 &amp; 9, and tricyclic pyranopyrazolopyridine 10a–c. These compounds were screened for their antibacterial activity against four bacterial strains. The promising candidates 4a, 4b, 4c, 7, 9, and 10c exhibited minimum inhibitory concentrations ranging from 0.98 to 31.25 μg/mL. The in silico ADME properties for the active compounds exhibited similar physiochemical properties, with compound 9 demonstrating the best likeness and no inhibition effect on the popular drug metabolism enzyme CYP. Molecular docking simulations highlighted compounds 9 and 10c as potent antibacterial agents via DNA-gyrase inhibition

Synthesis of new multi-functionalized Schiff base derivatives based on vanillic acid: Antimicrobial activity, photophysical, DFT calculations and in-silico study

The paper reports the synthesis of novel multi-functional Schiff base derivatives (S1-S7) via Steglich esterification, thoroughly characterized by standard spectroscopic methods (1H NMR, 13C NMR, FT-IR and Mass spectrometry) and elemental analysis technique. Density Functional Theory calculations (including FMOs’, MEP, IR and UV–Visible), photophysical, molecular docking simulations, and in-vitro antimicrobial assays were employed to study the structure and reactivity of synthesized compounds. The study highlights significant antimicrobial activity of certain derivatives, which aligns with computational predictions. UV–Visible study identifies various transitions like π→π*, n→π* occurring in the system aligning with the theoretical absorption spectra. Biological studies reveal that compounds S1, S2 and S5 exhibit significant potency for antimicrobial investigation correlating with the computational study. Further, the calculated HOMO-LUMO band gap for S1-S7 molecules (3.29 eV) suggest their insulating nature. Notably, MEP study shows negative electrostatic potential near nitro group and the positive potential near alkyl groups indicating preferable site for electrophilic and nucleophilic attack, respectively. Moreover, molecular docking was implemented to computationally screen the multi-functionalized Schiff base along with molecular dynamics simulation including MM-PBSA energy calculation in order to discover the reasonable physiological significance ensuring stability of binding interactions of relevant molecules.

Chiral FeNC single-atom nanozymes with multi-enzyme activity for dye degradation

The application of single-atom nanozymes in the removal of organic dye pollution by advanced oxidation process (AOPs) have been widely concerned. However, the application of single-atom nanozymes in AOPs is rarely reported. In this work, a kind of Fe-and nitrogen-codoped carbon (Fe-N-C) with peroxidase-like and laccase-like activities was prepared by calcining Fe-doped MOF, then the chiral peptides were introduced into single-atom nanozymes, and chiral single-atom nanozymes (L-Au@FeNC) were successfully prepared. The L-Au@FeNC can effectively activate PMS to degrade different kinds of organic dyes and also shows high cycle stability. In addition, the results of quenching experiment and electron paramagnetic resonance (EPR) test show that 1O2 produced during PMS activation plays an important role in the degradation of organic dyes, and O2·-, ·OH, and SO4·- are also produced during PMS activation, suggesting that the degradation of selected organic dyes include radical and non-radical pathways. It should be noted that L-Au@FeNC showed higher activity than D-Au@FeNC in enzyme-like activity (laccase-like and peroxidase-like) experiment and organic dye degradation, the results of molecular docking simulation indicated that it may be due to the better binding force of L peptide to the substrate of enzyme-like reaction and organic dye than D peptide. This chiral single-atom nanozymes provide a new idea for the application of organic dye degradation and enzyme-like catalysis design.

Evaluation of anticancer activity of some new hybrids of 1,3,4-oxadiazole tethered cinnamamides

A series of novel hybrids of 1,3,4-oxadiazole tethered cinnamamides was synthesized and characterized spectroscopically using 1H-NMR, 13C-NMR, and HR-MS. The synthesized compounds were screened for their anticancer activity using MTT (in vitro) assay involving different cancer cell lines such as MCF-7, MDA-AMB-231, DU-145, and PC-3. Among the tested compounds, compound 23 showed percentage inhibition against MCF-7 breast cancer cell lines reaching 30.23 %, whereas compound 21 exhibited an inhibition of 30.99% against prostate cancer cell lines (PC-3). The highly active seven compounds were further assessed to determine IC50 values against MCF-7 and PC-3 cell lines. Of which, compound 8 showed potent inhibition of 1.08 µM. None of the compounds exhibited any cytotoxicity toward normal cells. Structure-activity relationship analysis indicated the influence of electron-withdrawing functional groups on the anticancer activity, positively. This has been further supported by molecular modeling studies such as DFT analysis and molecular docking simulation. Pharmacokinetics ADME properties and drug likeliness are also determined, establishing the compounds druggability. Thus, the synthesized derivatives could be promising leads for further optimization to achieve novel anticancer agents.

Betalains from Opuntia stricta peels: UPLC-MS/MS metabolites profiling, computational investigation, and potential applicability as a raw meat colorant

Given consumers', environmental and sustainability apprehensions, the meat industry investigated the natural colorant resources. As proof, betalain, Opuntia stricta peels (OSP) pigment, is premeditated in the meat industry. Here, OSP betalains were qualitatively profiled using UPLC-MS/MS, and 7 metabolites were identified: 6 betacyanins and a betaxanthin (arginine-betaxanthin). Molecular docking simulations of cyclo-Dopa-5-O-β-glucoside, as the core betacyanins structure, and the arginine-betaxanthin, displayed the lowest free energies of binding at -8.1 and -7.6 Kcal/mol, respectively. These compounds inhibit the L. monocytogenes replication and transcription processes by targeting dihydrofolate reductase (DHFR). Then, OSP extracts (0.003, 0.006 and 0.012 %) were incorporated in the raw refrigerated beef meat, and compared to Allura red E129 at 0.002 % for 14 days. By the end of storage, OSP at 0.012% decreased the chemical oxidation, enhanced the sensory traits, and improved the instrumental color. In addition, chemometrics could distinguish between all samples linking oxidative and microbiological variables to sensory/instrumental color attributes.

Unraveling the impact of tungsten disulfide quantum dots on human serum albumin conformational dynamics and fibrillation pathways: An integrated multi-spectroscopic, biochemical, and molecular docking investigation

Herein, the intricate molecular interplay between human serum albumin (HSA) and tungsten disulfide quantum dots (WS2 QDs) was probed using spectroscopic techniques and sophisticated molecular simulation methods. Fluorescence spectroscopy demonstrated that under physiological conditions, WS2 QDs forge a non-fluorescent ground-state complex with HSA, facilitated by hydrogen bonding and van der Waals forces, ultimately resulting in the static quenching of the protein's intrinsic fluorescence. Complementary site competition experiments and molecular docking simulations reinforced a precise 1: 1 binding stoichiometry, predominantly targeting HSA's Site I. Three-dimensional fluorescence spectroscopy revealed that WS2 QDs perturb the HSA polypeptide backbone, subtly modifying the microenvironment surrounding aromatic amino acid residues. This alteration was further corroborated by circular dichroism spectroscopy, marked by a decrease in helical content and a transition towards irregular peptide conformations. Thermal stability assays illuminated the reduced thermal resilience of the HSA − WS2 QD complex. Laser confocal microscopy coupled with thioflavin T staining yielded compelling evidence that WS2 QDs effectively inhibit amyloid fibril formation in both HSA and lysozyme, underscoring their potential as potent anti-amyloidogenic agents. This comprehensive study offers pivotal insights into multifaceted impact of WS2 QDs on protein structure and function, thereby expanding their horizon of potential applications within the burgeoning field of nanomedicine.