Binding Affinity Values Research Articles

Mechanistic Insights into the interaction between aldehyde aroma compounds and β-Casein through Multi-Spectroscopy and molecular dynamics

The interaction between proteins and aroma compounds significantly impacts cheese flavor retention during processing. However, it is still unknown how cheese proteins and the aldehyde aroma compounds (AACs) interact. This study aims to clarify the interaction mechanisms between the AACs (benzaldehyde, 2-methylpropanal, 2-methylbutanal and 3-methylbutanal) and β-casein (β-CN) using SPME-GC/MS, multi-spectroscopy techniques, and molecular dynamics simulations. The results reveal notable variations in the binding abilities of the four AACs and β-CN, with the strongest binding observed for 3-methylbutanal. Specifically, the binding affinity (Ka) values between β-casein and benzaldehyde, 2-methylpropanal, 2-methylbutanal, and 3-methylbutanal are 2.26 × 103, 1.78 × 103, 2.03 × 103, and 2.52 × 103 M−1, respectively, indicating moderate binding affinity. Additionally, the quenching rate constants (Kq) for interactions with these compounds are 2.57 × 1011, 2.92 × 1011, 3.74 × 1011, and 4.81 × 1011 M−1s−1, significantly exceeding the collisional quenching limit, suggesting specific interactions. The interactions between the four AACs and β-CN occur through irreversible covalent bonding, primarily involving hydrogen bonds and hydrophobic interactions. The quenching mechanism of β-CN and the four AACs is static, which leads to changes in the secondary structure and microenvironment of β-CN. Molecular docking and dynamics simulations confirm that hydrogen bonds and hydrophobic interactions are the key driving forces for the binding of β-CN with the four AACs, and contribute to the stability of the composite system.

Screening of Natural Compounds as Inhibitor of Mpro SARS-CoV-2 Protein; A Molecular Dynamics Approach.

New strains of SARS-CoV-2 are continually emerging worldwide. Recently, WHO warned of a severe new wave in Europe. Current vaccines cannot fully prevent reinfection in vaccinated individuals. Given this issue, recent research focuses on new antiviral candidates with high efficacy and minimal side effects. Screen natural compounds as inhibitors of Mpro SARS-CoV-2 protein using molecular dynamics. In this study, we have screened the potential of plant-based natural anti-viral compounds. A library of the 579 compounds was generated using currently available literature and online databases. All these compounds were screened based on their binding affinities as predicted by molecular docking analysis and compounds having binding affinity values ≤ -10 Kcal/mol were considered for analysis. Furthermore, from physicochemical assessment, drug-likeness initially nine compounds were identified as the antiviral targets for the selected viral proteins. After ADMET analysis and simulations, the compound 9064 with the lowest RMSD, Coul-SR interaction energy (-71.53 kJ/mol), and LJ-SR energy (-95.32 kJ/mol) was selected as the most stable drug candidate against COVID-19 main protease Mpro. The ΔG value, calculated using MMGBSA also revealed strong binding of the compound with Mpro. The selected antiviral compound 9064 is an antioxidant flavonoid (Catechin or Cianidanol), which was previously known to have significant immunomodulatory, anti-inflammatory, and antioxidant properties. Considering the limitations of currently available vaccines, our study may provide new insight into potential drugs that may prevent SARS-CoV-2 infection in humans.

Molecular Docking of Brassicasterol Inhibition from Green Mustard Plant (Brassica Chinensis Var. Parachinensis) with Cytochrome P450 in Treating Chagas Disease

The aim of this study was to evaluate the potential of brassicasterol found in mustard greens as a cytochrome P450 inhibitor using a computational approach. The research method involved the use of various software such as PyRx, Pymol, Protein Plus, Protein Data Bank (PDB), and Lipinski's rule to analyze the molecular interactions and physicochemical characteristics of brassicasterol. The analysis results showed that brassicasterol has a significant affinity for cytochrome P450, with binding affinity values reaching -8.5, -8.4, and -8.2. RMSD analysis also showed that the brassicasterol-cytochrome P450 complex showed good stability, with RMSD values ranging from 0 to 2.832. The use of Protein Plus software illustrated the interaction between brassicasterol and cytochrome P450, while Lipinski analysis showed that brassicasterol meets the expected physicochemical criteria to be a chagas disease drug candidate, such as a molecular mass of 353, having one hydrogen bond donor and acceptor, and having a log P of 2.2 and a molar reactivity of 99.08. These findings provide new insights into therapeutic development in treating chagas disease using mustard green extract and brassicasterol as a cytochrome P450 inhibitor, but further study is needed to verify the potential of brassicasterol as a chagas disease drug.

Acetylcholinesterase – glucose-regulated protein 78 binding site prediction, a hope to cure neurological disorders such as Alzheimer’s disease

Cerebral amyloid plaques in the brain define the elderly neuralgic disorder, Alzheimer’s disease (AD). The enzyme Acetylcholinesterase (AChE) was reported to play a vital role in AD. It was shown that AChE induces amyloid fibril formation forming highly toxic AChE-Amyloid-β (Aβ) complexes. AChE can accelerate amyloid formation, and its inhibition could prevent such alterations to the enzyme. Understanding the proteostasis of AChE and its binding site to cellular chaperone GRP78 (Glucose-regulated protein 78) would help find a treatment for AD. In this study, the state of the art computational tools were utilized to predict the binding location of AChE that can stably associate with the cellular chaperone, GRP78. Sequence comparison along with molecular docking predicts two binding locations on AChE (C69–C96 and C257–C272) that could bind to GRP78 substrate binding domain β (SBDβ). The analysis of the docking data suggests that the former location has the best average binding affinity value (-12.16 kcal/mol) and average interaction pattern (13.9 ± 3.5 H-bonds, 5.5 ± 1.4 hydrophobic contacts, and 1.4 ± 1.2 salt bridges).

Interaction of Coumarin, Daphnetin, Fraxetin from Natural Materials with Carbanoic anhydrase II in Inhibiting Autosomal Recessive Osteopetrosis Disease

This article explores the interaction of Coumarin compounds and their derivatives obtained from natural extracts with Carbonic anhydrase II protein in inhibiting Glaucoma computationally. This research method includes modeling using software such as Pymol, Pyrx, Protein Plus, and Lipinski Rule of Five. The results showed Binding Affinity and RMSD of Coumarin, Daphnetin, and Fraxetin compounds with Carbonic anhydrase II with strong interaction. Protein Plus analysis was used to visualize the interaction that occurred between the compound and the Carbonic anhydrase II protein, in addition to the Lipinski Rule of Five test results, which showed results that were in accordance with the rules and met the drug criteria. These results indicate that Coumarin, Daphnetin, and Fraxetin compounds as Carbonic anhydrase II inhibitors have the potential to inhibit glaucoma. Daphnetin compound is the best inhibitor seen from the Binding Affinity value of -6.9, -5.8, and -5.5, as well as the results of Daphnetin's Lipinski Rule of Five data. However, further research is needed to validate this computational study.

Synthesis of nanohybrid consisting of taurine derived carbon dots and nanoceria for anticancer applications

Here, we first synthesized carbon dots (CDs) from taurine and then a nanohybrid with ceria (CeO2) nanoparticles using thermal decomposition method for checking their antineoplastic efficacy against human triple negative mammary carcinoma cells, MDA-MB-231. The in vitro study demonstrated significant dose-dependent antineoplastic activity of the nanohybrids within a range of concentration from 10 to 50 μg/mL after 48 h of treatment. The cellular morphology analysis clearly depicted substantial amount of cell death which seems to stem from increased intracellular reactive oxygen species (ROS) production. However, the maximum anticancer activity of the nanohybrid as compared to bare CDs and CeO2 is supposed to be due to the combined anticancer effect of both CDs and CeO2 (a well-established antitumor agent). Further we have performed molecular docking study to reveal the anticancer mechanism of CDs which exhibited high binding capacity towards several proapoptotic and antiapoptotic protein molecules. The binding affinity values were found to be – 8.7 kcal/mol, – 7.9 kcal/mol, – 9.6 kcal/mol, – 9.5 kcal/mol, – 12 kcal/mol and – 11.1 kcal/mol for BAD, BCl-2, p53, Caspase-8, Caspase-9 and Caspase-3 respectively. Taken together, our synthesized CDs-CeO2 nanohybrid could be thought as a potential anticarcinogenic option in the field of breast cancer therapeutics.

Exploring Natural Compounds Targeting the Bacterial SHV Protein to Combat Antibiotic Resistance: A Biocomputational Study

Background: Antibiotic-resistant (AR) bacteria are rapidly spreading worldwide, posing a serious threat to antibiotic efficacy. Bacterial infections have emerged as a persistent threat following decades of antibiotic use. Sulfhydryl variable (SHV) is a well-known bacterial enzyme linked to AR. SHV has a high degree of genetic diversity, resulting in the existence of numerous distinct variants. Methods: The PyRx AutoDock VINA was used to conduct in-silico screening of a natural compound library to assess their interaction with the SHV-1 protein. SwissADME web tools were used to predict the physicochemical, drug-likeness, and ADMET properties of the selected compounds.Result: The compounds PSCdb00708, PSCdb00149, PSCdb00698, and PSCdb00175 bind strongly to the SHV-1 protein and interact strongly with the SHV-1 active site residues, as well as having several amino acid residue interactions in common with avibactam. These compounds exhibited higher binding affinity values than avibactam. Furthermore, these compounds demonstrated no violation of drug-likeness.Conclusion: The compounds PSCdb00708, PSCdb00149, PSCdb00698, and PSCdb00175 can be employed as SHV-1 inhibitors in the management of AR. However, experimental validation is required to optimize them as SHV-1 inhibitors.Keywords: Antibiotic-resistant; Antibiotic; Virtual screening; AutoDock; SHV-1 protein

Metal Ion‐Endows Orange‐Red Light Fluorogenicity of an Imine‐Linkage Probe Embracing Simple Electron Donor‐Acceptor Units

AbstractSelectively tracking and quantifying Al3+ ions is a significant concern to the scientific communities. In the present article, an imine‐linkage electron donor‐acceptor system, DSAN, (E)‐5‐(diethylamino)‐2‐(((2‐hydroxy‐4‐nitrophenyl)imino)methyl)phenol has been introduced which shows Al3+ ions endows red light fluorogenicity which could be utilized for sequential and detection of Al3+ ions and picric acid (PA) in both solid and liquid phases. Upon addition of Al3+ ions into the DSAN solution, an orange‐red fluorescence is noticed at 604 nm caused by the formation of Al3+ ions chelated DSAN complex having detection and quantification limit 0.2 μM and 0.62 μM respectively in dimethylformamide (DMF) medium. The complex formation is found to be a 1 : 1 stoichiometric ratio as evident from Job's plot analysis. Also, the binding affinity value is found to be 3.24×104 M−1 demonstrating a high affinity of DSAN towards Al3+ ions. This orange‐red fluorescence of Al3+ ions chelated DSAN complex solution is quenched due to the introduction of PA. A super handy paper‐strips‐based detection tool also been fabricated utilizing DSAN which could be employed to track trace amounts of Al3+ ions in the solid state. The mechanism involved in the detection of Al3+ ions is elucidated by density functional theoretical analysis.

Design, Synthesis, Biological Evaluation, and In Silico Study of N‐(Pyridin‐2/3‐yl)alkanamide Derivatives as Quorum Sensing Inhibitors Against Pseudomonas aeruginosa

AbstractThe effectiveness of treating bacterial infections is seriously jeopardized by the emergence of bacterial resistance to chemical therapy. The development of biofilm in bacteria is one of the main causes of resistance to antimicrobial drugs. By developing new antibiofilm medications, quorum sensing (QS) inhibitor was developed as an alternate therapy. QS inhibition, which focuses on the QS signaling pathway, obstructs cell–cell communication. The aim of this work is to develop newer QS inhibitors against Pseudomonas aeruginosa. N‐(Pyridin‐2/3‐yl)alkanamide derivatives were designed as QS inhibitors, and these designed molecules were synthesized. QS inhibitor activity was evaluated for the synthesized compounds (3a–l, 4a–h). The highest QS inhibitor activities for compounds 3k, 4a, and 4c were 11.66 ± 0.11, 14.66 ± 0.15, and 10.66 ± 0.05 mm, respectively. Subsequent molecular docking analyses exhibited moderate to good binding affinity values between −7.1 and −9.3 kcal/mol. Using the in silico method, the physicochemical characteristics of these prepared compounds were examined. Additionally, molecular dynamic simulation was employed to gain a deeper comprehension of stability of the protein and ligand complexes of compounds 3k, 4a, and 4c. The overall findings of the study indicated that N‐(pyridin‐2/3‐yl)alkanamide derivatives might be significant for the development of newer QS inhibitors.

Chemical Compositions and Antimicrobial and Mosquito Larvicidal Activities of the Leaf Essential Oils of Goniothalamus yunnanensis W.T.Wang and G. touranensis Ast: Experimental and In Silico Approaches.

The current research describes a phytochemical analysis and antimicrobial activity of essential oils extracted from the leaves of two Vietnamese Annonaceae species Goniothalamus yunnanensis W.T.Wang and G. touranensis Ast. By the GC-FID/MS (gas chromatography-flame ionization detection/mass spectrometry) analyses, sesquiterpene hydrocarbons accounted for the highest percentage of 68.22 % in G. yunnanensis leaf essential oil with bicyclogermacrene (31.03 %) and (E)-caryophyllene (21.12 %) being the main compounds. G. touranensis leaf essential oil was dominated by monoterpene hydrocarbons (57.08 %) with p-cymene (19.95 %) and α-pinene (16.82 %) being the major compounds. By the microdilution broth susceptibility assay, two oil samples showed strong antibacterial effects on the Gram-positive bacteria Enterococcus faecalis ATCC51299, Staphylococcus aureus ATCC29213, and Bacillus cereus ATCC11778 with the MIC values of 16-64 μg/mL. They also inhibited the growth of the yeast Candida albicans ATCC 60193 with the same MIC value of 128 μg/mL. From the vector-based intervention approach, both oil samples showed strong mosquito larvicidal activity against four-instar larvae of Aedes aegypti and Ae. albopictus with the 24 h LC50 values of 16.75-27.60 μg/mL and 24 h LC90 values of 24.31-46.18 μg/mL. Docking results indicated that bicyclogermacrene and p-cymene exhibited the highest ΔG (binding affinity) values of -8.208 and -6.799 kcal/mol with the olfactory binding proteins (OBPs) of Ae. aegypti and Ae. albopictus, respectively.

A Comparative Study of Molecular Docking Analysis Study of Novel 13-Oxabicyclo[9.3.1]pentadecane, 15-chloro- and 3-Pyridinemethanol, 5-hydroxy-4-(methoxymethyl)-6-methyl-, hydrochloride from endophyte Asaialannensis against Multi Drug Resistant gene

The rising incidence of Multi-Drug Resistant (MDR) bacterial strains poses a grave threat to global public health. In the present study, two potential novel purified compounds, 13-Oxabicyclo[9.3.1]pentadecane,15-chloro- and 3-Pyridinemethanol, 5-hydroxy-4-(methoxymethyl)-6-methyl-, hydrochloride, isolated from the endophyte Asaialannensis, were docked with MDR genes and explored the binding affinities and interactions. The study involved the computational analysis of the binding modes and binding energies of the two novel compounds against a panel of bioactive ligands against the active sites of the bacterial Penicillin-Binding Protein 1b (PBP 1b) targetMDR genes with Easy Dock Vina Software. The docking results revealed that both 13-Oxabicyclo[9.3.1]pentadecane, 15-chloro- and 3-Pyridinemethanol, 5-hydroxy-4-(methoxymethyl)-6-methyl-, hydrochloride exhibited promising binding affinities and interactions with MDR genes. The comparative analysis suggested that these novel compounds may possess the capability to inhibit MDR gene activity effectively, offering a potential solution to combat drug-resistant bacterial infectionswith binding affinity values falling within the range of -6.1kcal/mol to -5.1kcal/mol.

In silico Pharmacodynamics, Antineoplastic Activity and Molecular Docking of two Phytochemicals Isolated from Thymelaea microphylla

Background: The lead compounds isolated from medicinal plants constitute a matrix for research and discovery of new drugs using in silico study and molecular docking. Objective: This work explores the in silico study and the molecular docking of two rare phytochemicals, namely Microphynolide A (1) and Microphynolide B (2), isolated from the Saharan medicinal plant Thymelaea microphylla (Thymelaeaceae family). Methods: In the current work, several integrated web-based in silico pharmacokinetic tools were used to estimate the druggability of two isolated phytochemicals. In addition, molecular docking was conducted using AutoDockVina 4.2 to study the binding interactions with the targets predicted employing the PharmMapper server. The toxicological study was evaluated using ProTox-II online server. DFT methods were utilized to evaluate some physicochemical properties of structures, vibrational wavenumbers, and molecular electrostatic potentials. Results: Molecules (1) and (2) showed good ADMET profiles and antineoplastic activity. Also, they exhibited non-toxicity and belong to the Toxicity class VI (LD50 >8000 mg/kg) with immunotoxic activity. A good correlation was observed between the experimental and theoretical IR spectra, with no negative values in the theoretical spectra indicating the high stability of these compounds. Docking simulation studies against protein receptors Sulfotransferase 1A1 (PDB ID: 1LS6) and Angiogenin (PDB ID: 1B1I) displayed good binding affinity values of -5.8 and -6.8 kcal/mol, respectively, with number of H-bonding interactions. Furthermore, the control molecules p-Nitrophenol (pNP), Dopamine, Axitinib and Bevacizumab displayed values of binding energies of -6.7, -6.7, -6.9 and -6.3 Kcal/mol, respectively. Conclusion: This study provides evidence supporting that the two molecules could be effective drugs to inhibit cancer cells and did not show any acute toxicity or mutagenic effects.

Unraveling the molecular interactions and antioxidant mechanism of β-lactoglobulin with aloe’s hydroxyanthracene derivatives: A focus on aloin and aloe-emodin

Aloe dairy products have occupied a certain market share, and the interaction between the small bioactive molecules contained in aloe and milk proteins during product processing profoundly affects the performance of dairy products. In this study, two typical and potentially dangerous bioactive small molecules of aloe, aloin (AA) and aloe-emodin (AE), were selected to investigate their interaction mechanism with β-lactoglobulin (β-La). Computer simulations showed that AA/AE had the potential to form complexes with β-La, and the β-La-AA system exhibited a stronger binding affinity than the β-La-AE system. Fluorescence analysis showed that the binding affinity values of AA to β-La at 298 K were deduced to be (4.184 ± 1.06) × 104 M−1, meaning medium-strength interactions, comparatively, AE to β-La was weaker, were deduced to be (3.15 ± 1.25) × 103 M−1. In addition, the thermodynamic analysis found that ΔH0 and ΔS0 were positive in both the β-La-AA system and the β-La-AE system, which implies that the main driving force for the combination of AA/AE and β-La to form the ground state complex is the hydrophobic force. The conformation changes in β-La brought about by binding to AA/AE may alter the properties and functions of the protein, such as surface hydrophobicity and oxidation resistance. Analysis shows that β-La is potentially present in whey as an AA/AE carrier during the production of aloe milk.

IN SILICO IDENTIFICATION OF BREADFRUIT PLAN COMPOUNDS (Artocarpus atilis) AGAINST ANGIOTENSIN-CONVERTING ENZYME 2 AS A CANDIDATE MODEL OF COVID-19 INHIBITORS

The spread of COVID-19 has continued to grow rapidly worldwide. This disease is characterized by the presence of severe respiratory syndrome disorders in humans. The ACE2 receptor is the gateway for the COVID-19 virus to target cells, where it is expressed in airway epithelial and vascular endothelial cells. Breadfruit (Artocarpus altilis) contains active flavonoids. Flavonoid derivatives found in breadfruit include artonin-E, cycloaltilisin-7, cycloaltilisin, isocyclomorusin, cyclomorusin, cyclomulberrin, isocyclomulberrin, cyclocommunal, morusin, quercetin and artocarpin. This study aimed to determine the flavonoid derivative of breadfruit (Artocarpus altilis), which has the most effective potential against the ACE2 receptor, as a candidate inhibitor of the COVID-19 virus in silico. The results showed that of the eleven flavonoid derivatives of breadfruit (Artocarpus altilis) tested, 3 compounds gave the lowest binding affinity value, namely cycloaltilisin -8.79 kcal/mol, cyclomulberrin -8.95 kcal/mol, and artocarpin -9.30. kcal/mol compared to Chloroquine -7.67 kcal/mol and Hydroxychloroquine -7.22 kcal/mol. The predicted results of the Lipinski Rule of Five showed that the 3 compounds and the comparison drug met the Ro5 rule. The compounds cycloaltilisin, cyclomulberin, and artocarpine have antiviral activity, as indicated by the Pa value in the range of 0.5<Pa<0.7. Cycloaltilisin, cyclomulberin and artocarpine are the most effective compounds to be developed as candidates for COVID-19 inhibitors. Keywords: Breadfruit, ACE-2, Covid-19, In Silico

The leaf essential oils of Meiogyne virgata (Blume) Miq., M. vietnamica Jaikhamseub, T.A.Le & Chaowasku, and Orophea polycarpa A.DC.: Chemical composition, antimicrobial activity, molecular docking, and toxicity profiling

The present study aims to describe the chemical composition of essential oils from three Vietnamese Annonaceae species, Meiogyne virgata, M. vietnamica, and Orophea polycarpa, and their antimicrobial activity. Essential oils were extracted by hydro-distillation. From the GC-FID/MS (gas chromatography-flame ionization detection and mass spectrometry) analysis, the leaf essential oil of M. virgata was reported to contain the major compound germacrene D (42.48%). Spathulenol (24.51%), bicyclogermacrene (18.58%), β-selinene (11.14%), and germacrene D (8.20%) can be seen as the main compound in M. vietnamica leaf essential oil. α-Phellandrene (39.35%), bicyclogermacrene (13.07%), β-phellandrene (10.87%), and limonene (8.27%) represented O. polycarpa leaf essential oil. Essential oil of M. virgata leaves exhibited strong antimicrobial activity against the Gram (+) bacterium Bacillus subtilis ATCC 5230, the Gram (-) bacterium Escherichia coli ATCC 8739, and the fungus Aspergillus niger ATCC 9587 with the same MIC value of 16 μg/mL. The docking method showed that germacrene D has the ΔGbinding (binding affinity) values of –6.68, –5.265, and –5.602 kcal/mol with the proteins E. coli DNA gyrase, B. subtilis TasA, and A. niger PhyA, respectively. Alkyl and pi-alkyl interactions are the main contributors to the binding affinity between the studied proteins and ligands. Furthermore, germacrene D is predicted to have low toxicity and is not active against any of the considered organ targets.

The potential of Sonneratia caseolaris mangrove leaves extract as a bioactive food ingredient using various water extract

Background Sonneratia caseolaris, known as the red pidada, has been widely utilized by the Indonesian. S. caseolaris leaves contain various active compounds, contributing to their popularity in the treatment of various diseases. Mangrove leaves are also known to exhibit very high antioxidant activity. This study aims to assess the antioxidant activity of S . caseolaris leaves extracted using different solvents. The resulting extract was evaluated for antioxidant activity by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (DPPH) techniques. Methods Analysis of total flavonoids, total phenols, identification of active compounds with Liquid Chromatography High Resolution Mass Spectrometry (LC-HRMS), and bioinformatics were also carried out to obtain temporary conclusions about the antioxidant activity of S. caseolaris leaf extract. Results The results indicated that S. caseolaris leaves extracted with methanol and distilled water exhibited the highest antioxidant activity compared to other extracts. The analysis of total flavonoids and total phenols yielded results consistent with the antioxidant activity tests. LC-HRMS results identified three compounds in all S. caseolaris leaf extracts with antioxidant activity, namely Tempo, Choline, and Betaine. Tempo demonstrated a higher antioxidant activity than Choline and Betaine, as indicated by the binding affinity values in the bioinformatics analysis. Conclusions It is evident that S. caseolaris leaf extract has the potential to serve as an effective an antioxidant agent. Further research is needed to elucidate confirm the potential compounds in Sonneratia caseolaris leaves water extract interact with the target protein Keap1. S. caseolaris, in order to utilize them as active components in food and enhance antioxidant consumption among consumers.

The potency of <i>Elaeocarpus grandiflorus </i>Leaf Extract as Anti-obesity: <i>in vivo </i>and <i>in silico</i> Study

The research aims to determine the effect of ethanol extract of Elaeocarpus grandiflorus leaves extract as anti-obesity by in vivo and silico computational models. The pre-and -post-tests were carried out on 20 female Wistar rats, divided into 4 groups. The control group (K) received no treatment and the experimental groups were treated with E. grandiflorus extract of 200 mg/kg BW (P1), 400 mg/kg BW (P2), and 800 mg/kg BW (P3) for 14 days. The body weight, abdominal circumference, and abdominal fat mass were measured on Day 1 and Day 15. The results showed differences in body weight (p=0.02), abdominal circumference (p=0.01), and abdominal fat mass (p=0.00). In silico exploration, bioactive compounds of rutin, orientin, luteolin, vitexin, iso orientin, isovitexin, kaempferol, and quercetin were identified, and targeted ELAVL1, IGF1R, CREB1, AKT1, and PIK3R1 of the AMPK signaling pathway that involved in the anti-obesity mechanism. The high binding affinity values was rutin-EVAL1 (-9.3), orientin-ELAVL1 (-8.3), and quercetin- IGFR1 (-8.2). It can be concluded that the ethanol extract of E. grandiflorus leaves has the potential to be developed as an anti-obesity agent.

Synthesis, characterization, biological evaluation and molecular docking study of some novel phenoxy methyl linked 1,2,3-triazole derivatives bridged with amide functionalities via ‘click chemistry’ approach

Herein, a new series of phenoxy methyl linked 1,4-disubstituted 1,2,3-triazole derivatives (SR1–SR16) was synthesized by click reaction and copper-catalyzed Huisgen [3 + 2] cycloaddition in the presence of copper sulphate and sodium ascorbate. All the newly synthesized compounds were characterized via Mass, 1H NMR, 13C NMR, FT-IR spectroscopy, and elemental analysis and evaluated for their antimalarial and antimicrobial activities. Among the synthesized compounds, SR12 containing naphthyl substituent is found to be the most active compound with IC50 of 18.60 μM in antimalarial activities and SR7 and SR9 were found to exhibit good antimicrobial activity at 600.83 μM and 614.12 μM concentration respectively. The antimalarial activity of the synthesized compounds was further supplemented by molecular docking studies against the PfDHFR (PDB ID- 3QGT) receptor, revealing that the remarkable binding affinity values and key interactions as compared to the standard reference Chloroquine. The drug-likeness properties of these compounds were supported by predicted pharmacokinetics.

Assessing the Efficacy of Acanthoic Acid Isolated from Acanthopanax koreanum Nakai in Male Infertility: An In Vivo and In Silico Approach.

Acanthoic acid, a diterpene isolated from the root bark of Acanthopanax koreanum Nakai, possesses diverse pharmacological activities, including anti-inflammatory, anti-diabetic, gastrointestinal protection, and cardiovascular protection. This study is the first to investigate the egg-hatching rates of Drosophila melanogaster affected by acanthoic acid. Notably, male flies supplemented with 10 μM acanthoic acid exhibited a strong increase in hatching rates compared with controls under adverse temperature conditions, suggesting a potential protective effect against environmental stressors. Molecular docking simulations revealed the binding affinities and specific interactions between acanthoic acid and proteins related to male infertility, including SHBG, ADAM17, and DNase I, with binding affinity values of -10.2, -6.8, and -5.8 kcal/mol, respectively. Following the docking studies, molecular dynamic simulations were conducted for a duration of 100 ns to examine the stability of these interactions. Additionally, a total binding energy analysis and decomposition analysis offered insights into the underlying energetic components and identified key contributing residues.

Phenolic Acid-β-Cyclodextrin Complexation Study to Mask Bitterness in Wheat Bran: A Machine Learning-Based QSAR Study.

The need to solvate and encapsulate hydro-sensitive molecules drives noticeable trends in the applications of cyclodextrins in the pharmaceutical industry, in foods, polymers, materials, and in agricultural science. Among them, β-cyclodextrin is one of the most used for the entrapment of phenolic acid compounds to mask the bitterness of wheat bran. In this regard, there is still a need for good data and especially for a robust predictive model that assesses the bitterness masking capabilities of β-cyclodextrin for various phenolic compounds. This study uses a dataset of 20 phenolic acids docked into the β-cyclodextrin cavity to generate three different binding constants. The data from the docking study were combined with topological, topographical, and quantum-chemical features from the ligands in a machine learning-based structure-activity relationship study. Three different models for each binding constant were computed using a combination of the genetic algorithm (GA) and multiple linear regression (MLR) approaches. The developed ML/QSAR models showed a very good performance, with high predictive ability and correlation coefficients of 0.969 and 0.984 for the training and test sets, respectively. The models revealed several factors responsible for binding with cyclodextrin, showing positive contributions toward the binding affinity values, including such features as the presence of six-membered rings in the molecule, branching, electronegativity values, and polar surface area.