Affinity Values Research Articles

Evaluation of in silico anticancer activity of some striazine derivatives as VEGFR2 inhibitors

The s-triazine derivatives have been shown to have diverse biological activities, especially anticancer activity. Fifty s-triazine derivatives were screened for anticancer activity through inhibition of VEGFR2 (vascular endothelial growth factor receptor-2) by molecular docking method using AutoDock Vina software. Compounds 20 and 40 showed the strongest interactions among all tested compounds with the binding affinity values of -10.8 and -10.5 Kcal/mol, respectively compared to reference drugs Gedatolisib (-9.1 Kcal/mol) and Paclitaxel (-7.8 Kcal/mol) at the active site of VEGFR2. These compounds established one carbon-hydrogen bond at amino acid HIS1026, specifically exhibiting better electrostatic and hydrophobic interactions than the reference drugs Gedatolisib and Paclitaxel. Moreover, compounds 20 and 40 also showed interactions with the VEGFR2 receptor that resemble the reference drug Gedatolisib at amino acids such as ARG1027, ASP1046, and HIS1026. Therefore, these compounds could be a potential lead molecule for anticancer activity.

Generation and reactivity of gas-phase phenyloxenium ion

Phenyloxenium ion (POI) is an important intermediate in organic reactions, however, its generation and reactivity have not been extensively investigated. In this study, POI is produced in the gas phase by electrospray ionization tandem mass spectrometry (ESI-MS/MS), isolated for gas phase ion-molecule reactions, and used theoretical calculations to reveal mechanisms to those reactions. It forms adduct ions with H2O, methanol, ethanol, benzene, and toluene, although the structures of the adduct ions are not well-resolved. In contrast, ortho-cyclization with nitriles has been verified by the reaction with acetonitrile and theoretical calculation. Further, Hydride transfer reaction during the reaction with tetrahydrofuran in the gas phase led to experimental values of the hydride affinity and electronic state of POI. Electron transfer studies revealed that the ionization potential of phenoxy radical locates in the range of 8.01–9.19 eV, in line with the calculated value of 8.60 eV for the singlet state POI.

In silico determination of fenthion, permethrin, and carbaryl as FFAR2 inhibitors: Type 2 diabetes mellitus pathomechanism study

Background: In the last few decades, many studies have shown that pesticides have a close relationship with increasing blood glucose levels and the incidence of diabetes. Some examples of pesticides include fenthion, permethrin, and carbaryl. Recently, free fatty acid receptor 2 (FFAR2) was identified as having a critical function in preventing insulin resistance. Activation of FFAR2 will reduce fat accumulation and induce glucagon-like peptide 1 (GLP-1) secretion, which plays an important role in regulating type 2 diabetes mellitus (T2DM) prevention.Objective: This study aims to determine a comparison of the binding ability between fenthion, permethrin, and carbaryl to FFAR2 protein for predicting the mechanism of pesticide toxicity to T2DM through an in silico study.Methods: This is an exploratory bioinformatic study. The protein structure was FFAR2 receptor (UniProt: O15552), while the ligand was fenthion (PubChem CID: 3346), permethrin (PubChem CID: 40326), and carbaryl (PubChem CID: 6129). This molecular docking was conducted in October 2022 using Asus X202XE with Intel® Core™ i3-3217U CPU equipped with BIOVIA Discovery Studio, AutoDockTools, and AutoDock Vina. Results: The binding affinity values generated after docking between fenthion, permethrin, and carbaryl with FFAR2 indicate that the binding affinity comparison is permethrin < carbaryl < fenthion. This explains that permethrin could form a stronger bond with FFAR2 protein than other pesticides. However, the visualisation results of the form of bond interactions show that permethrin does not bind to the active site of FFAR2, so it could not be called an inhibitor. This is different from fenthion and carbaryl, which could bind to several amino acid residues on the active site of FFAR2 and have the potential to become inhibitors.Conclusion: Carbaryl is a pesticide with the strongest FFAR2 inhibitor. Carbaryl could cause type 2 DM through its inhibitory pathway to FFAR2.

Synthesis and in-vitro anti-proliferative with antimicrobial activity of new coumarin containing heterocycles hybrids

A series of new coumarin-N-heterocyclic hybrids, coumarin-quinolines 7a–e, coumarin-acridines 10b,c and coumarin-neocryptolepines 13b,c were synthesized and evaluated for their anticancer and antimicrobial activities. The structures of all synthesized hybrids were confirmed by FT-IR, 1H-NMR, 13C-NMR, and MS spectrometry. The anti-proliferative activity of hybrids 7a–e, 10c and 13c were bio-evaluated using MTT-assay against colon (CaCo-2), lung (A549), breast (MDA-MB-231), and hepatocellular carcinoma (HepG-2) human cancer cell lines using doxorubicin as a reference drug. The results demonstrated that, all hybrids displayed moderate to good anti-proliferative activity against the cell lines. The most active hybrids were 7a–d and 10c against CaCo-2 cancer cell line with IC50: 57.1, 52.78, 57.29, 51.95 and 56.74 µM, and selectivity index 1.38, 1.76, 2.6, 1.96 and 0.77; respectively. While, 7a,d were potent against A549 cancer cell line with IC50: 51.72, 54.8 µM and selectivity index 1.5, 0.67; respectively. Moreover, 7c showed the most potency against MDA-MB-231 cancer cell line with IC50: 50.96 µM and selectivity index 2.20. Interestingly, docking results revealed that binding energy of the current compounds showed marked affinity values ranging from -6.54 to -5.56 kcal with interactions with the reported key amino acid SER 79. Furthermore, the antimicrobial activity of the synthesized hybrids 7a–e, 10b,c, 13b and 13c were evaluated against Gram‐positive and Gram‐negative bacterial and fungal strains. The hybrids 10b, 13b, 10c, and 13c exhibited broad-spectrum antibacterial activity against E.coli, S. mutans, and S. aureus with MIC from 3.2 to 66 µM, this hybrids also displayed antifungal activity against C. albicans with MIC values ranging from 0.0011 to 29.5 µM. In-silico investigation of the pharmacokinetic properties indicated that tested hybrids had high GI absorption, low Blood Brain Barrier (BBB) permeability in addition to cell membrane penetrability.

In Silico Activity Prediction and Docking Studies of the Binding Mechanisms of Levofloxacin Structure Derivatives to Active Receptor Sites of Bacterial Type IIA Topoisomerases

The need for new antimicrobial agents (AntAg) is driven by the persistent antibiotic resistance in microorganisms, as well as the increasing frequency of pandemics. Due to the deficiency of AntAg, research aimed at developing speedy approaches to find new drug candidates is relevant. This study aims to conduct an in silico study of the biological activity spectrum as well as the molecular binding mechanisms of four structurally different forms of levofloxacin (Lvf) with bacterial topoisomerases targets of type IIA (DNA gyrase and topoisomerase IV) to enable the development of drugs with an improved characterization of the safety profile. To achieve this goal, a number of software products were used, such as ChemicPen v. 2.6, PyMol 2.5, Avogadro 1.2.0, PASS, AutoDockTools 1.5.7 with the new generation software Autodock Vina. These software products are the first to be made available for visualization of clusters with determination of ligand-receptor pair binding affinity, as well as clustering coordinates and proposed mechanisms of action. One of the real structures of Lvf, a decarboxylated derivative, was obtained with tribochemical (TrbCh) exposure. The action spectrum of molecular ligands is described based on a Bayesian probability activity prediction model (PASS software Version 2.0). Predicted and real (PMS and RMS) molecular structures of Lvf, with decreasing levels of structural complexity, were translated into descriptors via Wiener (W), Balaban (Vs), Detour (Ip), and Electropy € indices. The 2D «structure-activity» diagrams were used to differentiate closely related structures of levofloxacin. PMS and RMS were visualized as 3D models of the ligand-receptor complexes. The contact regions of RMS and PMS with key amino acid residues—SER-79, DT-15, DG-1, DA-1—were demonstrated. The intra- and inter-molecular binding sites, data on free energy (affinity values, kcal/mol), the binding constant Kb (M−1), and the number of clusters are presented. The research results obtained from the presented in silico approach to explore the spectrum of action find quantitative “structure-activity” correlations, and predict molecular mechanisms may be of applied interest for directed drug discovery.

Inhibition potential against acetylcholinesterase of commercial and extracts of capsaicin and dihydrocapsaicin by in vitro and in silico studies

The present research investigates the amount of capsaicin and dihydrocapsaicin in three parts of chili extracts (pericarp, seeds, and placenta). Moreover, inhibition potential of capsaicin and dihydrocapsaicin, and chili extracts against AChE were also investigated in vitro and in silico study. The results show that placenta extract had more capsaicin (3818.72 mg/kg DW) and dihydrocapsaicin (2788.37 mg/kg DW) than other extracts. The inhibition potential of dihydrocapsaicin against AChE was higher than that of capsaicin and chili extracts. Which corresponded to the Ki value of dihydrocapsaicin (0.85 mM) higher inhibition potential than that of capsaicin (1.20 mM). The stronger interaction of dihydrocapsaicin than capsaicin at the active site of AChE was also supported by the binding affinity value (−7.8 kcal/mol for dihydrocapsaicin and −7.3 kcal/mol for capsaicin). However, the inhibition modes of dihydrocapsaicin and capsaicin were mixed-type inhibition against AChE. Besides, dihydrocapsaicin and capsaicin were surrounded by aromatic amino acids in the active site of AChE, which caused an increase in fluorescence intensity (FI). A similar increase in FI was also observed in the chili extracts (pericarp, seeds, and placenta). Our results show that capsaicinoids (capsaicin and dihydrocapsaicin) from chili extracts are natural inhibitors of AChE and may be applied to therapeutic Alzheimer's disease.

In-Silico Analysis of Polyphenol Compounds in Pomegranate Fruit (Punica granatum L.) Peel Potential as type 2 Antidiabetes Mellitus

Diabetes mellitus is a disease characterized by increased blood sugar levels due to insulin resistance caused by the uncontrolled expression of the protein tyrosine phosphatase 1B (PTP1B). Several compounds that inhibit PTP1B have been studied, including polyphenol. Many studies have been conducted on diabetes medicines based on natural ingredients, including the pomegranate fruits (Punica granatum L). This study aims to test the inhibitory activity of polyphenolic compounds in pomegranate peel (gallic acid, caffeic acid, ellagic acid, chlorogenic acid, apigenin, quercetin, pelargonidin, and cyanidin) against PTP1B through molecular docking. The 3D structures of polyphenolic compounds were obtained from the PubChem database, while PTP1B was from the Protein Data Base. Molecular docking simulations were carried out using AutoDock Vina and several supporting softwares, such as Biovia Discovery Studio Client 4.1, AutoDockTools 1.5.6, PyMOL, and LigPlot. Molecular docking results showed that polyphenolic compounds from pomegranate peel have good inhibitory potential against PTP1B. It is proven by the binding affinity value for PTP1B, which is low and negative, namely in the range -6.4 to -8.4 kcal/mol, and the inhibition constant in the range 0.69 to 20,12 µM. The presence of phenol and carboxylic acid groups in polyphenol compounds can strengthen ligand-protein complexes through hydrogen bonds, especially with the amino acid residues Gln221 and Cys215. The potential of polyphenolic compounds as antidiabetics is also supported by van der Waals interactions and π-π stacking interactions with PTP1B. Based on the molecular docking test that has been carried out, it can be concluded that the polyphenolic compounds in pomegranate peel have the potential to act as type 2 anti-diabetes mellitus.

Molecular dynamics simulations assisted investigation of phytochemicals as potential lead candidates against anti-apoptotic Bcl-B protein

Due to the multifarious nature of cancer, finding a single definitive cure for this dreadful disease remains an elusive challenge. The dysregulation of the apoptotic pathway or programmed cell death, governed by the Bcl-2 family of proteins plays a crucial role in cancer development and progression. Bcl-B stands out as a unique anti-apoptotic protein from the Bcl-2 family that selectively binds to Bax which inhibits its pro-apoptotic function. Although several inhibitors are reported for Bcl-2 family proteins, no specific inhibitors are available against the anti-apoptotic Bcl-B protein. This study aims to address this research gap by using virtual screening of an in-house library of phytochemicals from seven anti-cancer medicinal plants to identify lead molecules against Bcl-B protein. Through pharmacokinetic analysis and molecular docking studies, we identified three lead candidates (Enterolactone, Piperine, and Protopine) based on appreciable drug-likeliness, ADME properties, and binding affinity values. The identified molecules also exhibited specific interactions with critical amino acid residues of the binding cleft, highlighting their potential as lead candidates. Finally, molecular dynamics simulations and MM/PBSA based binding free energy analysis revealed that Enterolactone (CID_114739) and Piperine (CID_638024) molecules were on par with Obatoclax (CID_11404337), which is a known inhibitor of the Bcl-2 family proteins. Communicated by Ramaswamy H. Sarma

Virtual Screening, Pharmacokinetic Prediction, Molecular Docking and Dynamics Approaches in the Search for Selective and Potent Natural Molecular Inhibitors of MAO-B for the Treatment of Neurodegenerative Diseases

This research aims to find natural product compounds that have the potential to act as MAO-B inhibitors that are useful in the treatment of neurodegenerative diseases, through the stages: a) Virtual Screening, b) Molecule Docking, c) Pharmacokinetic and toxicity prediction, and d) Simulation approach Molecular dynamics.The research steps include the following steps: a) searching for molecules in the ZINC15 data base that are similar to the natural ligand molecule (safinamide) obtained from the protein data bank (PDB code: 2v5z) and the control ligand L-DOPA. A total of 481 molecules were downloaded from the data base and then molecular docking was carried out using the autodock program on the MAO-B target in the 2v5z receptor. After carrying out the docking analysis, 48 ligand molecules were selected which had a binding affinity (DG/kcal/mol) that was smaller than the DG of the natural ligand and the control ligand and nine (9) ligand molecules were taken to be tested: (i) ligand-ligand interactions MAO-B with discovery studio, (ii) Absorption, Distribution, Metabolism and Excretion properties with SwissADME and (iii) toxicity using PROTOX-II. Molecular dynamics simulations were carried out to determine the stability of ligands in proteins. Ligand complex [CC(C)c1ccc(NC(=O)Cn2cnc3c2c(=O)n(C)c(=O)n3C)cc1]-2v5z was chosen to simulate for 100 ps. The results of the molecular docking study showed that there were 9 molecules that had binding affinity values that were smaller than the binding affinity of the natural ligand and the control ligand. Ligand and residue interactions are dominated by hydrogen bonds, donor-donor and pi-pi stacked interactions. Based on SwissADME, the Blood Brain Barrier (BBB) permeant on ligand number 1, 2, 3, 5, 6, and 9 shows that it is orally active and cannot pass through the BBB and will not cause any side effects, whereas ligand number 4, 7, 8, 10, and 11 can cross the BBB and may cause side effects. Based on the results of toxicity prediction (PROTOX-II), it is known that there are four (4) ligands in class V, five (5) ligands in class IV and the rest in class II. Hepatotoxicity, carcinogenicity, and Phosphoprotein (Tumor Suppressor) p53 in eleven ligands are predicted to be inactive and have a small probability. The stimulated [CC(C)c1ccc(NC(=O)Cn2cnc3c2c(=O)n(C)c(=O)n3C)cc1]-2v5z complex apparently still shows ligand-protein fluctuations so that its conformation is still unstable.

Design, synthesis and molecular docking study of coumarin pyrazoline derivatives against MCF-7 breast cancer cell line

A new eight series of 3-(2-oxo-2H-chromen-3-yl)-5-(substituted phenyl)-1H-pyrazole-1-carbaldehyde derivatives (9–16) were designed and created from coumarin-chalcone derivatives (1–8). The structures of the derivatives were established by using melting point, mass spectrum, IR, 1HNMR, and 13C NMR spectroscopic methods. In vitro antiproliferative activities were evaluated against MCF-7 breast cancer cell line using Microculture Tetrazolium (MTT) assay. The results showed that the compounds 9, 12- 14 has a moderate activity against MCF-7 breast cancer cell line with IC50 61.44, 70.11, 22.6 and 25.99 µg/mL respectively, while the compounds 10,11, 15 and 16 were found to be inactive against studied cell line within IC50 > 100 µg/mL. The possible binding interaction between studied compounds (9–16) and human ER-α (PDB ID: 1ERR) were studied by molecular docking. The results revealed that only the compounds 11 and 16 form π -H interaction with ER-α (PDB ID: 1ERR) within the highest negative values of binding affinity -7.04260 and -7.17308 kcal.mol-1 respectively than the other compounds, while Raloxifene used here as a positive control form a strong ionic bonding with Asp 351 within the binding affinity -9.61928 kcal/mol which is more negative value than the studied compounds.

STUDY MOLECULES DOCKING OF ALKALOIDS IN KRATOM ON SEROTONIN TRANSPORTER (SERT), NOREPINEPHRINE TRANSPORTER (NET), AND MONOAMINE OXIDASE (MAO)

Kratom (Mitragyna speciosa Korth) is a tropical plant originating from Southeast Asia that predominantly contains alkaloid compounds and can potentially maintain levels of monoamine compounds in the body to treat depression. The study aimed to examine the potential of 8 alkaloid compounds in kratom as antidepressants towards four target proteins: Serotonin Transporter (SERT), Dopamine Transporter (DOPAT), Leucine Transporter (LEUT), and Monoamine Oxidase (MAO) via molecular docking. The Pyrx program is used with exhaustiveness 106 as the protocol, and the grid is adapted to the active site of each receptor. The affinity values ​​of the alkaloid compounds in kratom are mitragynine, 7-hydroxy mitragynine, speciociliatine, paynantheine, speciogynine, corynantheidine, mitraciliatine, and 9-hydroxycorynantheidine, for MAO were -7.1, -6.1, -5.7, -6.7, -5.7, -7.7, -5.7, and -5.7 kcal/ mole. All compounds bind to amino acid residues in the target protein through hydrogen and pi (π) bonds. All the tested alkaloid compounds have the potential to be re-uptake inhibitors SERT, DOPAT, LEUT, and Monoamine Oxidase (MAO).

Determination of phyto-moieties from the traditional therapeutic plant Boswellia serrata Roxb. extract against nosocomial pathogens: in vitro and silico approaches

IntroductionThe present study aimed to examine the in vitro antibacterial activity of Boswellia serrata solvent extracts against multidrug-resistant nosocomial pathogens isolated from skin and wound samples. MethodsB. serrata resin was acquired, and powdered; blended with five different extraction solvents. The collected bacterial isolates from wound and skin swabs were identified using biochemical profiling and classified according to their unique physiological and biochemical characteristics. Three isolated pathogens were exposed to antibiotic drugs via the disk dispersion assay, and the antimicrobial efficiency of the plant extract was assessed against the wound and skin infection-causing nosocomial bacterial pathogens. The qualitative and quantitative examination of plant extracts was carried out by mass spectra and 70 eV electron impact ionisation process. The 2D molecular interaction patterns between beta-lactamase protein and phytocompounds complexes were generated in DS viewer to understand the hydrogen bonding and hydrophobic interaction. ResultsThree antibiotic-resistant strains, Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii, were isolated and exposed to the extract of B. serrata. Plant extract at 60 µg proven effective against antibiotic-resistant strains of S. aureus, P. aeruginosa, and A. baumannii. In molecular docking studies, it was found that out of the 15 bioactive compounds detected from the plant extract, only three showed significant binding affinity to the bacterial-lactamase protein (AmpC). The auto dock results revealed different crucial affinity values of the bioactive compounds. Cholan-24-oic acid, 3,12-bis(acetyloxy) showed a Dock score of −8.6 kcal/mol for P. aeruginosa, −8.1 kcal/mol for A. baumannii, and −7.6 kcal/mol for S. aureus. Due to its strong binding affinity with antibacterial target proteins, it exhibits exceptional antibacterial properties. ConclusionThe findings confirmed bioactive constituents in B. serrata, with antibacterial activity against antibiotic resistance nosocomial pathogens.

Trust your Good Friends: Source-free Domain Adaptation by Reciprocal Neighborhood Clustering.

Domain adaptation (DA) aims to alleviate the domain shift between source domain and target domain. Most DA methods require access to the source data, but often that is not possible (e.g. due to data privacy or intellectual property). In this paper, we address the challenging source-free domain adaptation (SFDA) problem, where the source pretrained model is adapted to the target domain in the absence of source data. Our method is based on the observation that target data, which might not align with the source domain classifier, still forms clear clusters. We capture this intrinsic structure by defining local affinity of the target data, and encourage label consistency among data with high local affinity. We observe that higher affinity should be assigned to reciprocal neighbors. To aggregate information with more context, we consider expanded neighborhoods with small affinity values. Furthermore, we consider the density around each target sample, which can alleviate the negative impact of potential outliers. In the experimental results we verify that the inherent structure of the target features is an important source of information for domain adaptation. We demonstrate that this local structure can be efficiently captured by considering the local neighbors, the reciprocal neighbors, and the expanded neighborhood. Finally, we achieve state-of-the-art performance on several 2D image and 3D point cloud recognition datasets.

INHIBISI EKSTRAK DAUN SIRIH MERAH TERHADAP LIPASE PANKREAS SEBAGAI ANTIOBESITAS SECARA IN SILICO

A Obesity triggers the emergence of various degenerative diseases, such as stroke, heart disease, type 2 diabetes, and insulin resistance. Pancreatic lipase inhibitors are anti-obesity drug agents that work by inhibiting pancreatic lipase enzymes. This study aims to search and predict the inhibitory activity of pancreatic lipase from the active compound of red betel leaf. The research began with virtual screening of 60 test ligands, prediction of ligand stability and toxicity, validation method of molecular docking, molecular docking, 2D and 3D visualization. The results showed that benzethonium octyloxyacetate, salicylic acid beta-D-glucopyranosyl ester, and anthocyanins had the best potential in inhibiting pancreatic lipase enzymes based on virtual screening, ligand stability, ligand toxicity, energy affinity, number of hydrogen bonds with active site, bond distance, and constants inhibition (Ki). Benzethonium octyloxyacetate has an affinity value of -8 kcal/mol, has a hydrogen bond interaction on the His349 residue on the active site of the pancreatic lipase receptor (6KSM) with a bond distance of 2,94 Å and Ki value of 1,347 μM

Mangostenone Bioactive Compound from Garcinia mangostana L. as Antiviral Agent via Dual Inhibitors Against E6 HPV 16/18 Oncoprotein through Computational Simulation

HPV is a DNA virus from Papillomaviridae about 170 types have been identified and most of these viruses can triger cervial cancer disease. Types of HPV that can trigger cervical cancer consist of HPV-16 and HPV-18 with around 70% of cases, HPV-6 and HPV-11 only trigger genital warts. Types of HPV-16 and HPV-18 are high risk in triggering cervical cancer. High risk HPV types have the ability to interfere with the performance of tumor suppressors in cells through oncoprotein activity. E6 is a crucial oncoprotein because it allows degradation of tumor suppressors in host cells, E6 can be a major target in antiviral drug design. Inhibition of the E6 domain by antiviral candidate compounds is an important part of preventing the formation of the E6-p53 complex and preventing cancer development. Garcinia mangostana L. (Mangosteen) is a traditional medicine for treating bacterial, viral, fungal infections, as an antioxidant, and for degenerative diseases. This study aims to explore the potential of mangostenone compounds from Garcinia mangostana L. as HPV antivirals through inhibition of the E6 oncoprotein on HPV-16 and HPV-18 through in silico study. In silico analysis methods such as drug likeness, antiviral probability, docking simulation, chemical interaction analysis, and molecular visualization were used in this study to reveal HPV antiviral candidates from Mangostenone derivatives. Mangostenone derivative compounds from Garcinia mangostana L. can be antiviral candidates for HPV through a dual inhibitory mechanism by Mangostenone A. These compounds have strong activity through more negative binding affinity values and weak bonds such as hydrogen and hydrophobic bonds compared to other mangostenone derivative compounds.

Antibacterial and biofilm prevention metabolites from Acanthophora spicifera

Abstract Acanthophora spicifera harbors a diverse array of secondary metabolites with therapeutic potential. The aim of this study is to isolate and characterize secondary metabolites from A. spicifera and then evaluate the antiproliferation, antibacterial, and biofilm prevention properties, followed by an analysis of molecular docking experiments. By employing chromatographic analysis and NMR spectroscopy, the isolated compounds were, the known flavonol, 8-hydroxyquercetagetin (1), three recognized steroids cholest-4-ene-3,6-dione (2), cholest-5-en-3β-ol (3), and 5α-cholestane-3,6-dione (4), and 2-bromohexadecanoic acid (5). These compounds exhibited antimicrobial effects against various Gram-negative and Gram-positive bacteria with inhibition zones ranging from 6.5 ± 0.2 to 17.2 ± 0.12 mm and 7.0 ± 0.4 to 15.3 ± 0.60 mm, respectively. Compounds 1 and 2 inhibited biofilm formation in P. aeruginosa and S. aureus. Compounds 1–4 demonstrated binding affinity values between −7.5 and −9.4 kcal/mol to protein 1A0G. These binding affinity values were akin to that of amoxicillin, implying that one potential antibacterial mechanism of action of these compounds may involve the inhibition of bacterial cell wall synthesis. All compounds showed no toxicity against Artemia salina and weak activity against Lymphoma and Lewis lung carcinoma cell lines with LD50 > 100 μg/mL.

Synthesis, Activity Test and Molecular Docking of Novel Nitrophenylcalix[4]-2-methylresorcinarene Derivatives as Antimalarial Agent

This research involved the synthesis, antimalarial assay and molecular docking of novel nitrophenylcalix[4]-2-methylresorcinarene derivatives. Calix[4]-2-methylresorcinarene derivatives, i.e., 2N, 3N and 4N, were synthesized in a one-step reaction through the cyclo-condensation reaction between resorcinol and aldehydes, i.e., 2-nitrobenzaldehyde, 3-nitrobenzaldehyde and 4-nitrobenzaldehyde, respectively. The reaction was carried out through the reflux method with ethanol and hydrochloric acid 37% as the solvent and catalyst, respectively. The synthetic products were characterized using FTIR, 1H-NMR, 13C-NMR, and LC-MS spectrometers. Furthermore, the in vitro antimalarial assay was carried out against Plasmodium falciparum strain 3D7. The results showed that the 2N, 3N and 4N compounds were successfully synthesized in 86.4, 78.6 dan 95.7% yield, respectively. The antimalarial activity test of 2N, 3N and 4N gave IC50 values of 2.35, 1.68 and 1.79 µM, therefore, these compounds are classified as active antimalarial agents. Molecular docking performed against the PfLDH receptor showed that the 2N, 3N and 4N compounds had negative binding affinity values of -5.1, -6.1, and -6.0 kcal/mol and had specific interactions in the form of hydrogen bonds to the amino acid residues Arg109, Thr101 and Lys102 in the active site of the receptor. The molecular docking results agreed with the experimental antimalarial assay demonstrating the mechanism of action of nitrophenylcalix[4]-2-methylresorcinarenes as active antimalarial agents happened through the inhibition of the PfLDH receptor.

Pharmacology of Berberine and Its Metabolites, Is It the Natures Ozempic or Imatinib?

Background: Berberine, a naturally occurring alkaloid, is widely explored for several health benefits, including weight management and metabolic disorders. The major pharmacological action of berberine is reported to be by activation of AMP-activated protein kinase, while its other clinical outcomes are devoid of clear mechanism of action/s. Hence in this study a detailed pharmacology of berberine and its two major metabolites (berberrubine, and jatrorrhizine) in humans was evaluated using well established Insilco tools. Materials and Methods: The targets of berberine and its metabolites were identified in SwissTargetPrediction server and their affinity was assed using AutoDock vina 1.2.0. The binding pockets of the highest ligand receptor combinations was assessed using the PrankWeb: Ligand Binding Site Prediction tool. Results: Kinases, enzymes and family A GPCR’s were identified as the top three target category of berberine and its metabolites. ROCK2, PIK3CD, KCNMA1, CSF1R, and KIT were observed to be the high affinity targets of berberine and its metabolites with affinity values of <4 uM. The affinity of berberine and its metabolites against all AMPKs and lipid/glucose regulator targets (LDLR, DDP4 and PCSK9) were >10 uM. The IC50 value of berberine and its metabolites against ROCK2 was the least (<1 uM), while their other high affinity targets (PIK3CD, KCNMA1, CSF1R and KIT) showed IC50 values <5 uM. Conclusion: The diverse range of protein targets and the observed novel high affinity targets (ROCK2, PIK3CD, KCNMA1, CSF1R and KIT) offer valuable insights into the potential mechanisms of action and therapeutic effects of berberine and its metabolites in various disease conditions, which warrants validation in suitable efficacy analysis studies.

Oriented External Electric Field Modulated Superhalogen Characteristic and Photoelectric Properties of Al4N2 Cluster: A Density Functional Theory Study

AbstractDesigning superatoms with special structural and photoelectric properties is vital for the applications in multiple fields including condensed matter physics, nanomaterials science etc. In this study, the effects of an oriented external electric field (OEEF) on the geometry, electronic properties, photoelectron spectrum (PES), and nonlinear optical (NLO) response of the main group metal‐doped cluster Al4N2 were investigated using density functional theory (DFT) calculations. The results demonstrate that the OEEF has the capability to increase the value of the electron affinity (EA) of Al4N2 continuously and dramatically, transforming it into a member of superhalogens while maintaining its geometrical stability. Such an enhancement of the EA value of Al4N2 is attributed to the downward shift of the electronic spectrum under the effect of the OEEF. Strikingly, the relationship between the EA value of Al4N2 and the OEEF strength can be fitted by a perfect polynomial formula, which indicates that the OEEF can realize the accurate and continuous regulation of the electronic properties of Al4N2. In addition, the simulated PES of the Al4N2− cluster was observed to be blue shifted following the enhancement of the OEEF intensities, and the NLO response of the cluster can also be remarkably altered by the OEEF.

In Silico Study of Glyphosate Substitute against Rice Weeds as Bioherbicides Candidate

Weeds on rice plants have a lot of negative impacts on plant productivity. The majority of approaches in controlling weeds in rice used herbicides including the use of glyphosate as a synthetic herbicide. However, using glyphosate in the long-term results in soil and water pollution accumulation, resulting in decreased soil fertility. This study aims to find new herbicide candidates by mimicking glyphosate's mechanism in inhibiting EPSP synthase, ACCase and photosystem II found in three types of weeds (broad-leaved and grasses and sedges). Representatives of the three types are Monochoria vaginalis (broad-leaved weeds), Cyperus rotundus (sedges) and Eleusine indica (grasses). The PyRx AutoDoc Vina docked fourteen potential bioherbicide candidate compounds at specific sites. The binding affinity value is calculated and ranked to determine the best compound as a bioherbicide candidate. In predicting biological activity, the discovery studio visualized the interaction of each complex. Benzoate and Cinmethylin are the most potent compounds as bioherbicide candidates with binding affinities of -8.2 and -6.9 kcal/mol. This interaction shows 50-59% similarity with glyphosate, so this compound inhibits PEP synthesis, amino acid biosynthesis, photosynthesis and controlling weeds in rice plants.