Molecular Docking Calculations Research Articles

Specifically targeting antimicrobial peptides for inhibition of Candidatus Liberibacter asiaticus.

Huanglongbing (citrus greening) is a plant disease putatively caused by the unculturable Gram-negative bacterium Candidatus Liberibacter asiaticus (CLas), and it has caused severe damage to citrus plantations worldwide. There are no definitive treatments for this disease, and conventional disease control techniques have shown limited efficacy. This work presents an in silico evaluation of using specifically targeting anti-microbial peptides (STAMPs) consisting of a targeting segment and an antimicrobial segment to inhibit citrus greening by inhibiting the BamA protein of CLas, which is an outer membrane protein crucial for bacterial viability. Initially, a set of peptides with a high affinity toward BamA protein were screened and evaluated via molecular docking and molecular dynamics simulations and were verified in vitro via bio-layer interferometry (BLI). In silico studies and BLI experiments indicated that two peptides, HASP2 and HASP3, showed stable binding to BamA. Protein structures for STAMPs were created by fusing known anti-microbial peptides (AMPs) with the selected short peptides. The binding of STAMPs to BamA was assessed using molecular docking and binding energy calculations. The attachment of high-affinity short peptides significantly reduced the free energy of binding for AMPs, suggesting that it would make it easier for the STAMPs to bind to BamA. Efficacy testing in vitro using a closely related CLas surrogate bacterium showed that STAMPs had greater inhibitory activity than AMP alone. In silico and in vitro results indicate that the STAMPs can inhibit CLas surrogate Rhizobium grahamii more effectively compared to AMPs, suggesting that STAMPs can achieve better inhibition of CLas, potentially via enhancing the site specificity of AMPs.

A Novel One-Pot Three-Component Approach to Orthoaminocarbonitrile Tetrahydronaphthalenes Using Triethylamine (Et_3N) as a Highly Efficient and Homogeneous Catalyst Under Mild Conditions and Investigating Its Anti-cancer Properties Through Molecular Docking Studies and Calculations

An efficient and environmentally friendly method for the one-pot synthesis of ortho-aminocarbonitrile tetrahydronaphthalenes has been developed in the presence of triethylamine (Et3N) as a homogeneous catalyst. The multicomponent reactions of benzaldehydes, cyclohexanone and malononitrile were carried out under mild conditions to obtain some ortho-aminocarbonitrile tetrahydronaphthalene derivatives. A broad range of structurally diverse benzaldehydes were applied successfully, and corresponding products (4A-L) were obtained in good to excellent yields (87-98%) in very short times (10-25 minutes). The present approach provides several advantages including simple workup, high yields, very mild reaction conditions, short reaction times, little catalyst loading and not requiring specialized equipment. Furthermore, with the help of computational chemistry and drug design methods, the anti-cancer properties of these compounds were studied and investigated. All the synthesized compounds bind to an agonist at the active site of the 3A8P protein, which leads to the inactivation of this protein and produces beneficial effects during cancer treatment. In synthesized compounds, the ligands establish hydrogen bonds with leucine A:728 residues through nitrogen, which has a very special and vital role in biological sciences and pharmaceutical connections. In this study, it was found that these compounds have the potential to become an oral anti-cancer drug.

Synthesis of 1, 2-Disubstituted Benzimidazoles at Ambient Temperature Catalyzed by 1-Methylimidazolium Tetraflouroborate ([Hmim] BF_4) and Investigating Their Anti-ovarian Cancer Properties Through Molecular Docking Studies and Calculations

An environmentally benign method for the synthesis of 1, 2-disubstituted benzimidazoles by the reaction of aromatic aldehydes and o-phenylenediamines (OPD) in the presence of 1-methylimidazolium tetraflouroborate ([Hmim] BF4) at ambient temperature under green conditions is described. A broad range of structurally diverse benzaldehydes were applied successfully, and corresponding products were obtained in good to excellent yields in very short times. All products were identified by the melting points, 1H and 13C NMR techniques. Furthermore, with the help of computational chemistry and drug design methods, the anti-ovarian cancer properties of these compounds were studied and investigated. All the synthesized compounds bind to an agonist at the active site of the 6LAD protein, which leads to the inactivation of this protein and produces beneficial effects during ovarian cancer treatment. In this study, it was found that these compounds have the potential to become an oral anti-cancer drug.

Synthesis of R-GABA Derivatives via Pd(II) Catalyzed Enantioselective C(sp3)-H Arylation and Virtual Validation with GABAB1 Receptor for Potential leads.

GABA (γ-amino butyric acid) analogues like baclofen, tolibut, phenibut, etc., are well-known GABAB1 inhibitors and pharmaceutically important drugs. However, there is a huge demand for more chiral GABA aryl analogues with promising pharmacological actions. Here, we demonstrate the chiral ligand acetyl-protected amino quinoline (APAQ) mediated enantioselective synthesis of GABAB1 inhibitor drug scaffolds from easily accessible GABA via Pd-catalyzed C(sp3)-H activation. The synthetic methodology shows moderate to good yields, up to 74% of ee. We have successfully demonstrated the deprotection and removal of the directing group to synthesize R-tolibut in 86% yield. Further, we employed computation to probe the binding of R-GABA analogues to the extracellular domain of the human GABAB1 receptor. Our Rosetta-based molecular docking calculations show better binding for four R-enantiomers of GABA analogues than R-baclofen and R-phenibut. In addition, we employed GROMACS MD simulations and MMPB(GB)SA calculations to identify per-residue contribution to binding free energy. Our computational results suggest analogues (3R)-4-amino-3-(3,4-dimethylphenyl) butanoic acid, (3R)-4-amino-3-(3-fluorophenyl) butanoic acid, (3R)-3-(4-acetylphenyl)-4-aminobutanoic acid, (3R)-4-amino-3-(4-methoxyphenyl) butanoic acid, and (3R)-4-amino-3-phenylbutanoic acid are potential leads which could be synthesized from our methodology reported here.

Synthesis of (-) - 6,6'-dinitrohinokinin from hinokinin natural product and in silico and in vitro trypanocidal activity assessment

Chagas disease is a public health problem affecting approximately seven million people worldwide. Thus, there is a need to discover drugs for the adequate treatment of this disease because currently available drugs have serious side effects. Therefore, this study aimed to evaluate the in vitro trypanocidal activity of (-)-6,6'-dinitrohinokinin, obtained from the partial synthesis of (-)-hinokinin, on the trypomastigotes and amastigotes forms. For the trypomastigote assay, blood was collected from mice infected with Trypanosoma cruzi through cardiac puncture at the parasitemic peak. The results show that (-)-6,6'-dinitrohinokinin was effective against the trypomastigote forms, presenting an IC50 of 19.83 µM and lysis percentage values ​​of 78.4% and 69.4% at concentrations of 200 and 100 µM, respectively. Molecular docking calculations indicate that (-)-6,6'-dinitrohinokinin favorably interacts with the amino acids present in the active site of the protein trypanothione reductase, a typical target for anti-trypanosomal drug development. According to the results, the (-)-6,6'-dinitrohinokinin showed more significant trypanocidal activity with IC50 of 1.83 µM than benzonidazole positive control with IC50 of 53.2 µM, showing to be a prototype molecule promising for the development of a new antiparasitic drug.

Thai traditional medicines reduce CD147 levels in lung cells: Potential therapeutic candidates for cancers, inflammations, and COVID-19

Ethnopharmacological relevanceThe cluster of differentiation 147 (CD147) is identified as the signaling protein relevant importantly in various cancers, inflammations, and coronavirus disease 2019 (COVID-19) via interacting with extracellular cyclophilin A (CypA). The reduction of CD147 levels inhibits the progression of CD147-associated diseases. Thai traditional medicines (TTMs): Keaw-hom (KH), Um-ma-ruek-ka-wa-tee (UM), Chan-ta-lee-la (CT), and Ha-rak (HR) have been used as anti-pyretic and anti-respiratory syndromes caused from various conditions including cancers, inflammations, and infections. Thus, these medicines would play a crucial role in the reduction of CD147 levels. Aim of the studyThis article aimed to investigate the effects of KH, UM, CT, and HR for reducing the CD147 levels through in vitro study. Additionally, in silico study was employed to screen the active compounds reflexing the reduction of CD147 levels. Materials and methodsThe immunofluorescent technique was used to evaluate the reduction of CD147 levels in human lung epithelial cells (BEAS-2B) stimulated with CypA for eight extracts of KH, UM, CT, and HR obtained from water decoction (D) and 70% ethanol maceration (M) including, KHD, UMD, CTD, HRD, KHM, UMM, CTM, and HRM. ResultsUM extracts showed the most efficiency for reduction of CD147 levels in the cytoplasm and perinuclear of BEAS-2B cells stimulated with CypA. Phenolic compounds composing polyphenols, polyphenol sugars, and flavonoids were identified as the major chemical components of UMD and UMM. Further, molecular docking calculations identified polyphenol sugars as CypA inhibitors. ConclusionsUMD and UMM are potential for reduction of CD147 levels which provide a useful information for further development of UM as potential therapeutic candidates for CD147-associated diseases such as cancers, inflammations, and COVID-19.

Probing the inhibition of MAO-B by chalcones: an integrated approach combining molecular docking, ADME analysis, MD simulation, and MM-PBSA calculations.

Monoamine oxidase B (MAO-B), an enzyme of significant relevance in the realm of neurodegenerative disorders, has garnered considerable attention as a potential target for therapeutic intervention. Natural compounds known as chalcones have shown potential as MAO-B inhibitors. In this particular study, we employed a multimodal computational method to evaluate the inhibitory effects of chalcones on MAO-B. Molecular docking methods were used to study and assess the complicated binding interactions that occur between chalcones and MAO-B. This extensive analysis provided a valuable and deep understanding of possible binding methods as well as the key residues implicated in the inhibition process. Furthermore, the ADME investigation gave valuable insights into the pharmacokinetic properties of chalcones. This allowed them to be assessed in terms of drug-like attributes. The use of MD simulations has benefited in the research of ligand-protein interactions' dynamic behaviour and temporal stability. MM-PBSA calculations were also done to estimate the binding free energies and acquire a better knowledge and understanding of the binding affinity between chalcones and MAO-B. Our thorough method gives a thorough knowledge of chalcones' potential as MAO-B inhibitors, which will be useful for future experimental validation and drug development efforts in the context of neurodegenerative illnesses.

Hepatoprotective perspective of newly synthesized 3-(3,5-bis (tri fluoro methyl) phenyl)- 5-methyl-1-((1-methyl-1h-pyrrol-2-yl) methyl)-2-thioxoimidazolidin-4-one against diethyl nitrosamine induced liver injury in rats with molecular docking investigatio

The hepatoprotective effect of synthesized 3-(3,5-bis (trifluoromethyl) phenyl)-5-methyl-1-((1-methyl-1H-pyrrol-2-yl) methyl)-2-thioxoimidazolidin-4-one (3FL-M) was evaluated against diethyl nitrosamine-induced liver injury (DEN). Wistar rats were divided into 3 groups as: placebo (received 10% tween 80%), hepatotoxic control (injected with 200 mg/kg of DEN) and treatment (injected 200 mg/kg of DEN and received 50 mg/kg oral feeding of the synthesized 3FL-M). Half the number of the rats were sacrificed on 2nd week of the experiment, whereas the other half were sacrificed after 6 weeks. Blood was collected to run liver biochemical analysis, and to evaluate pro-inflammatory cytokines tumor necrosis factor-alpha TNF-α and interleukine6 IL-6. Liver sections were used to detect nuclear protein ki-67 and hepatocyte specific antibody HSA. 3FL-M was subjected to molecular docking calculations based on binding affinities towards TNF-α and IL-6. DEN-treated rats showed elevation in the liver serum enzymes as well as pro-inflammatory cytokines with clear destruction of the hepatic architecture, in contrast 3FL-M treated rats showed normalized liver enzymes and cytokines levels with resolution of the hepatocytes. Molecular modelling revealed that 3FL-M exhibited the significant affinities toward the binding pocket of the TNF-α and IL-6, however, further studies is recommended for developing it as a chemotherapeutic drug-like molecule.
 KEY WORDS: DEN, Hepatoprotective, TNF-α, IL-6, Molecular docking
 Bull. Chem. Soc. Ethiop. 2024, 38(3), 751-763. 
 DOI: https://dx.doi.org/10.4314/bcse.v38i3.16

Identification of a Novel Peptide with Alcohol Dehydrogenase Activating Ability from Ethanol-Induced Lactococcus lactis: A Combined In Silico Prediction and In Vivo Validation.

Alcohol dehydrogenase (ADH) is a crucial rate-limiting enzyme in alcohol metabolism. Our previous research found that ethanol-induced intracellular extracts of Lactococcus lactis (L. lactis) could enhance alcohol metabolism in mice, but the responsible compounds remain unidentified. The study aimed to screen potential ADH-activating peptides from ethanol-induced L. lactis using virtual screening and molecular docking calculation. Among them, the pentapeptide FAPEG might bind to ADH through hydrophobic interaction and hydrogen bonds, then enhancing ADH activity. Spectroscopy analysis further investigated the peptide-enzyme interaction between FAPEG and ADH, including changes in the amino acid residue microenvironment and secondary structural alterations. Furthermore, FAPEG could protect against alcoholic liver injury (ALI) in mice by reducing blood alcohol concentration, enhancing the activity of antioxidant and alcohol metabolism enzymes, and attenuating alcohol-induced hepatotoxicity, which was related to the activation of the Nrf2/keap1/HO-1 signaling pathway. The study provided preliminary evidence that the generation of ADH-activating peptides in ethanol-induced L. lactis has the potential in preventing ALI in mice using in silico prediction and in vivo validation approaches.

Expression, purification, and characterization of transmembrane protein homogentisate solanesyltransferase

Homogentisate solanesyltransferase (HST) is a crucial enzyme in the plastoquinone biosynthetic pathway and has recently emerged as a promising target for herbicides. In this study, we successfully expressed and purified a stable and highly pure form of seven times transmembrane protein Chlamydomonas reinhardtii HST (CrHST). The final yield of CrHST protein obtained was 12.2 mg per liter of M9 medium. We evaluated the inhibitory effect on CrHST using Des-Morpholinocarbony Cyclopyrimorate (DMC) and found its IC50 value to be 3.63 ± 0.53 μM, indicating significant inhibitory potential. Additionally, we investigated the substrate affinity of CrHST with two substrates, determining the Km values as 22.76 ± 1.70 μM for FPP and 48.54 ± 3.89 μM for HGA. Through sequence alignment analyses and three-dimensional structure predictions, we identified conserved amino acid residues forming the active cavity in the enzyme. The results from molecular docking and binding energy calculations indicate that DMC has a greater binding affinity with HST compared to HGA. These findings represent substantial progress in understanding CrHST’s properties and potential for herbicide development.Key points• First high-yield transmembrane CrHST protein via E. coli system• Preliminarily identified active cavity composition via activity testing• Determined substrate and inhibitor modes via molecular docking

Design, spectral, antibacterial and in-silico studies of new thiosemicarbazones and semicarbazones derived from symmetrical chalcones

A series of new Schiff bases of semicarbazones and thiosemicarbazones have been derived from the condensation of symmetrical chalcones with semicarbazide and thiosemicarbazide, respectively. Various physicochemical and spectroscopic approaches (UV, IR, 1H, and 13C NMR) were used to fully describe the newly synthesized compounds. Schiff base derivatives were screened against bacterial strains viz. Bacillus Subtilis and Escherichia Coli. The DFT approach was also used to analyze some sensitivity descriptors alike chemical potential (µ), electronegativity (χ), hardness (η), and electrophilicity index (ω). Molecular docking was used to determine binding affinity of compounds with the desired protein. Compounds were identified to be more effective against Bacillus Subtilis than E. Coli. The molecular docking calculations of compound (6) exhibited the escalated binding affinity of -8.01 kcal/mol and binds with the active amino acids (Glu57 and Asp162). The prediction of in silico ADME properties discovered that synthesized molecules acquire significant drug-likeness properties.

Prediction of Binding Pose and Affinity of Nelfinavir, a SARS-CoV-2 Main Protease Repositioned Drug, by Combining Docking, Molecular Dynamics, and Fragment Molecular Orbital Calculations.

A novel in silico drug design procedure is described targeting the Main protease (Mpro) of the SARS-CoV-2 virus. The procedure combines molecular docking, molecular dynamics (MD), and fragment molecular orbital (FMO) calculations. The binding structure and properties of Mpro were predicted for Nelfinavir (NFV), which had been identified as a candidate compound through drug repositioning, targeting Mpro. Several poses of the Mpro and NFV complexes were generated by docking, from which four docking poses were selected by scoring with FMO energy. Then, each pose was subjected to MD simulation, 100 snapshot structures were sampled from each of the generated MD trajectories, and the structures were evaluated by FMO calculations to rank the pose based on binding energy. Several residues were found to be important in ligand recognition, including Glu47, Asp48, Glu166, Asp187, and Gln189, all of which interacted strongly with NFV. Asn142 is presumably regarded to form hydrogen bonds or CH/π interaction with NFV; however, in the present calculation, their interactions were transient. Moreover, the tert-butyl group of NFV had no interaction with Mpro. Identifying such strong and weak interactions provides candidates for maintaining and substituting ligand functional groups and important suggestions for drug discovery using drug repositioning. Besides the interaction between NFV and the amino acid residues of Mpro, the desolvation effect of the binding pocket also affected the ranking order. A similar procedure of drug design was applied to Lopinavir, and the calculated interaction energy and experimental inhibitory activity value trends were consistent. Our approach provides a new guideline for structure-based drug design starting from a candidate compound whose complex crystal structure has not been obtained.

Docking Study on Caspase 3 Inhibitors As Potential Drugs For Traumatic Brain Cell Apoptosis

Background: Apoptosis of brain cells (neurons and glia) has a crucial role in humans' pathology of traumatic brain injury (TBI). So, a decrease in the apoptosis rate can potentially reduce the harmful effects and lead to better functional outcomes. Drug repurposing by computational methodologies like protein-ligand docking allows us to make drug discovery more efficient and less expensive. Objective: In the current study, we used the methodology to study the inhibitory effect of thousands of FDA/non-FDA approved, investigational compounds on caspase 3 as one of the most important members of the cell apoptosis pathway. Methods: Molecular docking and pharmacokinetic properties calculations were done. The molecular dynamics (MD) simulations of all complexes and free caspase 3 were carried out. We carried out docking experiments using in silico methods and docked a pool of medications to the active site of the human caspase-3 X-ray structure. The best compounds were selected and subjected to pharmacokinetic analysis, molecular simulation, and free energy calculations. Results: Finally, 6 components (Naldemedine, Celastrol, Nilotinib, Drospirenone, Lumacaftor, and R- 343) were selected as the best in terms of structural and pharmaceutical properties, low toxicity that can be administered orally for the preclinical and clinical future investigations.

Aging effects of titanium dioxide on Cu toxicity to Daphnia magna: Exploring molecular docking and significance of surface properties

Cosmetics and personal care products containing titanium dioxide nanoparticles (TiO2 NPs) may enter aquatic environments, where the surface coatings of TiO2 NPs may change with aging due to environmental factors such as light, and potentially affect their bioaccumulation and toxicity. This study examined how aging impacted the physicochemical properties of three commercially available TiO2 NPs and subsequent influence on the bioaccumulation and toxicity of copper (Cu) in Daphnia magna (D. magna). We demonstrated that aging significantly affected the hydrophobicity of TiO2 NPs, which affected their binding to water molecules and adsorption of Cu. Changes of bioaccumulation of TiO2 NPs and Cu in D. magna ultimately affected the activities of intracellular antioxidant enzymes such as SOD, CAT, GSH-Px, and the transmembrane protein Na+/K+–ATPase. Molecular docking calculations demonstrated that changes of activities of these biological enzymes were due to the interaction between TiO2 NPs, Cu, and amino acid residues near the sites with the lowest binding energy and active center of the enzyme. Such effect was closely related to the hydrophobicity of TiO2 NPs. Our study demonstrated the close relationship between surface properties of TiO2 NPs and their biological effects, providing important evidence for understanding the behavior of nanomaterials in aquatic environments.

Probing the interaction of an antiviral drug 8-methoxy-3-nitro-2-(4-methoxyphenyl)-2H-chromene (MNC) with DNA by experimental and computational approach

Deoxyribonucleic acid (DNA) is a major target in research pertaining to antiviral and anticancer therapies since it is the principal genetic material that controls vital biological functions. The complex relationship between calf thymus DNA (ct-DNA) and 8-Methoxy-3-nitro-2-(4-methoxyphenyl)-2H-chromene (MNC), an anticancer drug derivative of 2-aryl-3-nitro-2H-chromenes, is explored in this work. Using various spectroscopic methods such as fluorescence, circular dichroism (CD), UV–visible, isothermal titration calorimetry (ITC) experiment, and molecular docking calculations, this study elucidates the binding characteristics and affinity between MNC and ct-DNA. Through predominant groove binding and moderate intercalation, MNC demonstrates a complicated binding pattern with DNA at the minor groove, as shown by the UV–Vis spectra and emission-based dye displacement investigations. DNA undergoes a little conformational change that MNC induces, as shown by CD spectroscopy. The thermodynamics parameters such as the binding constant, binding enthalpy, and binding free energy of DNA-MNC interaction, as calculated by the ITC experiment, were approximately ∼ 104 M−1, −26 kcal mol−1, and 6 kcal/mol, respectively. The binding process is enthalpy driven implying a stabilizing contact of MNC with DNA and the entropic penalty (−TΔS = +20.1 kcal mol−1) points to a reduction in the degree of freedom of movement. The molecular docking investigation also estimates the similar interaction energy and binding locations of MNC with DNA. Interestingly, MNC attaches to the surface of the DNA via electrostatic interactions; a stronger attachment through van der Waals and hydrophobic contacts within the minor groove follows this. These studies are anticipated to provide researchers with important direction for designing new drug molecules for further biomolecular investigations.

Molecular modeling of novel 2-aminopyridine derivatives as potential JAK2 inhibitors: a rational strategy for promising anticancer agents

Janus kinase 2(JAK2) is a potential target for anticancer drugs in the treatment of numerous myeloproliferative diseases due to its central role in the JAK/STAT signaling cascade. In this study, the binding behavior of 2 amino-pyridine derivatives as JAK2 inhibitors was investigated by using multifaceted strategies including 3D-QSAR, molecular docking, Fingerprint analysis, MD simulations, and MM-PBSA calculations. A credible COMFA (q 2 = 0.606 and r 2 = 0.919) and COMSIA (q 2 = 0.641 and r 2 = 0.992) model was developed, where the internal and external validation revealed that the obtained 3D-QSAR models could be capable of predicting bioactivities of JAK2 inhibitors. The structural criteria provided by the contour maps of model were used to computationally develop more potent 100 new JAK2 inhibitors. Docking studies were conducted on the model data set and newly developed compounds (in-house library) to demonstrate their binding mechanism and highlight the key interacting residues within JAK2 active site. The selected docked complexes underwent MD simulation (100 ns), which contributed in the further study of the binding interactions. Binding free energy analyses (MMGB/PBSA) revealed that key residues such as Glu930, Leu932 (hinge region), Asp939 (solvent accessible region), Arg980, Asn981and Asp994 (catalytic site) have a significantly facilitate ligand-protein interactions through H-bonding and van der Waals interactions. The preliminary in-silico ADMET evaluation revealed encouraging results for all the modeled and in-house library compounds. The findings of this research have the potential to offer valuable recommendations for the advancement of novel, potent, and efficacious JAK2 inhibitors. Overall, this work has successfully employed a wide range of computer-based methodologies to understand the interaction dynamics between 2-amino-pyridine derivatives and the JAK2 enzyme, which is a crucial target in myeloproliferative disorders. Communicated by Ramaswamy H. Sarma

Investigating the antimicrobial and anti-inflammatory activities of novel thiophene derivatives by in-vitro studies, molecular docking, spectral analysis, and quantum chemical calculations

The rise of antibiotic-resistant pathogens and the widespread occurrence of inflammatory diseases have raised considerable global health concerns. Consequently, there is a critical need to formulate novel and potent drug candidates to counteract these pressing global threats effectively. Hence, this study presents a comprehensive investigation involving spectral (FT-IR, and 1H NMR) analysis, experimental, molecular docking, and quantum chemical calculations employing density functional theory (DFT) to fully characterize and identify the synthesized compounds (Thiosemicarbazide Schiff base (TSB), 4‑methoxy aniline Schiff base (ASB), Phenyl urea Schiff base (PSB) at the ωB97XD/6-311++G(2d,2p) level of theory. Noteworthy observations from the antimicrobial investigations against four different microorganisms: Staphylococcus aureus, Escherichia coli, Candida albicans, and Aspergillus niger, TSB and ASB displayed varying degrees of antimicrobial activity. Notably, they exhibited the most significant effect against Candida albicans and A. niger, showing promise in combatting fungal infections. In contrast, PSB demonstrated moderate to high antimicrobial activity against E. coli, ranging from 15 mm to 24 mm. Molecular docking studies further confirmed TSB's strong binding affinity against Candida albicans with -6.4 kcal/mol, indicating robust interaction with the target protein. TSB also exhibited reasonably good binding affinities of -5.5 kcal/mol and -5.1 kcal/mol against Aspergillus niger and E. coli, respectively. ASB and PSB displayed particularly strong binding affinities against specific microorganisms, making them potential candidates for further investigation as antimicrobial agents. Furthermore, investigation into anti-inflammatory activity revealed that PSB demonstrated the highest free radical scavenging activity, with a percentage of 62.39 % and an IC50 value of 41.83. ASB followed with a free radical scavenging activity of 58.71 % and an IC50 value of 67.62, while TSB exhibited a free radical scavenging activity of 57.79 % with an IC50 value of 72. These findings were consistent with molecular docking analysis, suggesting that TSB effectively interacts with the active sites of the target proteins, potentially modulating the inflammatory response. Interestingly, PSB showed superior free radical scavenging activity compared to ASB and TSB, indicating its potential as an effective anti-inflammatory agent.

Polygonum aviculare L.'s biological Activities: Investigating its Anti-Proliferative, Antioxidant, chemical properties supported by molecular docking study

In this study, two different solvent extracts of Polygonum aviculare L. collected from natural environment were evaluated in terms of their antioxidant properties, antiproliferative properties and interactions of the extract components with proteins, and were addressed in terms of their pharmacological potential and biological activities. The plant was extracted using two different solvents, and its biological activity levels were examined utilizing in vitro antioxidant and antiproliferative (cytotoxicity assay) assays. According to the results obtained, there was a variation in chemical composition between the water and methanol extracts of this plant. While “1,4:3,6-Dianhydro-.alpha.-d-glucopyranose” was determined with 2.78 as the major component of the water extract of the plant, “n-Hexadecanoic acid” was determined with 10.32 in the methanol extract. The antioxidant activity of the plant was evaluated according to both DPPH and ABTS methods. The results obtained in both methods were found to be close to each other. While the antioxidant activity value of the plant remained at a moderate level compared to the standard substance, it was observed that the activity value increased as the concentration increased. When the results were examined in terms of antiproliferative properties of aqueous and methanolic extracts, it was seen that only the water extract was active. In addition, among the molecules identified in the extracts, it was determined by molecular docking calculations that cyclododecane, which is the third most abundant component in the methanol extract, showed the highest biological activity. In the same time, the activities of chemicals found in Polygonum aviculare L. plant extract against a range of proteins, including the crystal structures of the following: bovine xanthine oxidedase (PDB ID: 3NRZ), human peroxiredoxin 5 (PDB ID: 1HD2), antibacterial FabH inhibitors (PDB ID: 4Z8D), estrogen receptor (PDB ID: 1A52), and the BRCT repeat region (PDB ID: 1JNX). Next, the compounds with the highest activity were analyzed for their ADME/T characteristics.

The impact of some metals, molecular docking and molecular dynamic calculations on glucose 6-phosphate dehydrogenase activity in Capoeta trutta (Heckel, 1843) tissue

The first enzyme of the pentose phosphate metabolic pathway is glucose 6-phosphate dehydrogenase (d-glucose-6-phosphate: NADP + oxidoreductase EC1.1.1.49; G6PD). G6PD has essential functions such as membrane lipid synthesis, ribose 5-phosphate, and NADPH production. In this study, the G6PD enzyme was purified from kidney, liver, and gill tissues of Capoeta trutta, one of the dominant fish species in the Euphrates-Tigris River System, and the in vitro effects of some metals (Ag+, Cd2+, Cu2+, Fe2+, Ni2+, Pb2+ and Zn2+) on the enzyme activity were investigated. For this purpose, firstly, the G6PD enzyme was purified from tissues using a 2′, 5′-ADP Sepharose 4B affinity column. The purity of the enzyme was checked by the SDS-PAGE method and a single band was seen in the gel. After the purity of the enzyme was determined, the effects of metals on the enzyme activity were determined using the spectrophotometric method. As a result of the study, it was determined that the Ag+ ion was the most potent inhibitor for C. trutta gill, kidney, and liver G6PD enzymes. Lastly, calculations were made to examine the activity of the glucose 6-phosphate dehydrogenase molecule against the G6PD enzymes. Afterwards, the interaction of the glucose 6-phosphate dehydrogenase molecule with the protein (PDB ID: 5JYU and 2BH9) with the highest activity was calculated in the range of 0–100 ns. Finally, ADME/T calculation was made to predict the effects and reactions of glucose 6-phosphate dehydrogenase molecule in human metabolism. This study explores the physiological functions and environmental sensitivities of G6PD in a dominant fish species, while also investigating its potential interactions and metabolic roles in humans. Understanding these aspects can contribute to environmental monitoring, fish health management, and even pharmaceutical development.

New 1,2,4-triazol-3-one derivatives with 4-fluorobenzene: Synthesis, characterization, DFT, antimicrobial-antiproliferative activities and molecular docking study

(E)-5-(4-fluorobenzyl)-4-((2-fluorobenzylidene)amino)-2,4-dihydro-3H-1,2,4-triazol-3-one (2F), (E)-5-(4-fluorobenzyl)-4-((3-fluorobenzylidene)amino)-2,4-dihydro-3H-1,2,4-triazol-3-one (3F) and (E)-5-(4-fluorobenzyl)-4-((4-fluorobenzylidene)amino)-2,4-dihydro-3H-1,2,4-triazol-3-one (4F) were synthesized and confirmed by FT-IR and 1H, 13CNMR spectroscopic methods. Theoretical study for compounds 2F-4F was performed by using DFT/B3LYP/6–311++G(d,p) method. The optimized structures, IR and NMR data, the frontier molecular orbitals (HOMO and LUMO) and the molecular electrostatic potential (MEP) map of compounds 2F-4F were calculated. In addition, newly synthesized compounds (2F-4F) were tested against eight bacteria and two yeast strains and their the minimum inhibitory concentration (MIC) values were determined. The MTT test was performed to measure the antiproliferative effects of the 2F-4F compounds on cell proliferation (NCI-60 screening methodology). Molecular docking calculations were performed to investigate ligand-protein interactions between the compounds (2F and 3F) and the Epidermal Growth Factor Receptor (EGFR) and the Vascular Endothelial Growth Factor Receptor (VEGFR1).