Π Inter-actions Research Articles

A handheld fluorescent platform integrated with a Sm(III)-CdTe quantum dot-based ratiometric nanoprobe for point-of-use determination of phosphate.

Phosphate (Pi) is crucial for various physiological processes and aquatic environments, which emphasizes the need for a simple, on-site sensor to promptly detect Pi for human health and environmental conservation. In this study, we propose a dual-emission ratiometric fluorescence sensor for highly sensitive and visual Pi detection. The sensor employs samarium ions (Sm3+) as a core component, with cadmium telluride quantum dots (CdTe QDs) and ofloxacin (OFL) serving as signal carriers. The CdTe-Sm(III)-OFL nanoprobe emits a purple fluorescence resulting from the red fluorescence of CdTe QDs and the blue-green fluorescence of OFL. The fluorescence of OFL is quenched by Sm3+ through fluorescence resonance energy transfer (FRET). Upon Pi interaction, the FRET process is disrupted due to the competitive Pi-Sm3+ binding, which leads to the fluorescence recovery of OFL while the red fluorescence of CdTe remains steady. This enables the construction of a ratiometric fluorescent sensor for Pi detection, manifesting as a color change from purple to blue. The sensor demonstrated a linear response for Pi detection within the range of 0.1-75 μM, with a low detection limit of 17.0 nM. By utilizing the distinct fluorescence responses of various physiological phosphates and employing chemometrics, this innovative dual-emission sensor accurately distinguishes among different physiological phosphates. Furthermore, a portable lab-on-paper device based on CdTe-Sm(III)-OFL, coupled with a smartphone-integrated mini-device, is developed for swift Pi detection using an ordinary smartphone. Analytical performance validated on environmental and biological samples demonstrates the sensor's excellent robustness and adaptability. This study introduces a pioneering approach to fabricate ratiometric fluorescence sensors and customize portable, cost-effective mini-devices for precise target detection, thus opening avenues for advanced sensing strategies in various applications.

Synthesis, design, biological activity, DFT study and molecular docking of new 1,2,4-triazine and 1,2,4-triazol derivatives bearing the phthalazine moiety

The present work aims to synthesise a series of new compounds with a combination of 1,2,4-triazine and 1,2,4-triazole with a phthalazine components that have been created from compound (M4). The structural formula of these new compounds was confirmed by FT-IR, 1HNMR , 13CNMR and Mass spectra. Density functional theory (DFT) simulations utilising the Gausean-9 programme were used to rationalise the mechanism of all novel compounds. They demonstrations that the energy gap between compounds (M8–M10) is 0.09951 a.u., 0.108133 a.u. and 0.9857 a.u., respectively, between HOMO and LOMO. The molecular docking analysis unveiled the existence of several derivatives exhibiting significant binding affinities and unique interaction patterns with the target proteins. Derivatives M8–10 have been identified as the most favourable candidates, demonstrating the highest binding energies and a diverse range of interaction types, such as hydrogen bonding and pi interactions, across various distances. Derivative (M8–10) exhibits the highest binding energy at S = -8.15, -8.18, or -8.28 Kcal/mol with the 2VAM receptor and -8.52, -8.78 and -9.04 Kcal/mol with the 2G1H receptor. The analysis of the inhibition of the growth values in different concentrations against both Escherichia coli and Bacillus subtilis bacteria compared with amoxicillin. The presented research obviously demonstrates that compounds (M8–10) can serve as promising candidates for alternatives to new medications. The empirical findings were consistent with the anticipated outcomes derived from the molecular docking analysis.

Effect of hydroxy groups on structural, electronic, and biological properties of methyl carbazate containing hydroxy benzaldehyde-based imines. A combined experimental and theoretical investigation

Interactions present in differently substituted hydroxy based imine derivatives were characterised and identified by the utilisation of spectroscopic techniques in conjunction with X-ray crystallography and theoretical computations. All the target compounds ‘a-c’ crystallises in monoclinic crystal system with P21/c and C2/c space groups. CH…Pi and Pi…Pi interaction are the characteristic interactions present in the target compounds ‘a-c’ The most significant contributions to the crystal packing were found using Hirshfeld surface analysis, and potential contact points were identified. H…H, O…H and C…H contacts and π stacking interactions are the dominant contacts observed in all the crystals these results showed that hydrogen bonding and hydrophobic interactions were significantly present. Furthermore, investigations related to calculations of the molecular electrostatic potential and frontier molecular orbital (highest occupied–lowest unoccupied) were carried out for the optimised structure. The HOMO-LUMO energy gap made it possible to determine the molecule's chemical hardness, chemical inertness, electronegativity, and electrophilicity index, which showed its possible kinetic stability and reactivity. The target compounds' predicted activity spectra (PASS) showed that these compounds exhibit significant Testosterone 17beta-dehydrogenase (NADP+) inhibition activity, with Pa 7.18–7.95. Finally, Testosterone 17beta-dehydrogenase (NADP+) (PDB-ID 3KLP) was used to conduct molecular docking investigations of compounds ‘a-c’. Due to their tiny size and lack of rigidity, which enable them to bind well at any position, a and b exhibit higher binding free energies of -7.08 and -7.00 kcal/mol and inhibition constants of 0.1 and 1.2 µM than compound c.

Sex toys for pleasure, but there are risks: In silico toxicity studies of leached Micro/Nanoplastics and phthalates

The widespread use of sex toys has sparked concerns about potential health risks associated with the leaching of micro/nanoplastics (M/NPs) and phthalates. In this in silico toxicity analysis, we investigated the immunotoxicity potential of compounds mechanically produced from sex toys. The research focuses on understanding their interactions with critical human cytochrome P450 enzymes (CYP34A and CYP2D6), which are central to drug metabolism and immune function. Four types of M/NPs (polyethylene terephthalate - PET, polyvinyl chloride - PVC, polydimethylsiloxane - PDMS, polyisoprene) and eight phthalates (Diethyl phthalate - DEP, Bis(4-methyl-2-pentyl) phthalate, Bis(2-methoxyethyl) phthalate, Benzyl butyl phthalate - BBP, Dibutyl Phthalate - DBP, Diethylhexyl phthalate - DEHP, Dinonyl phthalate - DNP, Di-n-octyl phthalate - DnOP) from sex toys were analyzed. Molecular dynamics and docking simulations were conducted to assess the binding affinity of these compounds to the enzymes. PET exhibited the highest toxicity, with a binding affinity of -8.3 kcal/mol and -8.9 kcal/mol for CYP3A4 and CYP2D6, respectively, surpassing control values (-7.8 kcal/mol and -6.3 kcal/mol). BBP showed considerable toxicity, binding strongly to CYP3A4 (-7.8 kcal/mol) and CYP2D6 (-9.1 kcal/mol). PDMS and DEP were the lowest toxic compounds in both groups. Molecular interactions revealed hydrogen bonds, pi interactions, and unfavorable donor-donor effects between compounds and specific amino acid residues within the enzymes. While these in silico findings provide insights, they underscore the need for comprehensive chemical analyses and absorption studies to validate health risks. This research emphasizes the necessity of evaluating the toxicity of M/NPs and phthalates from sex toys, promoting further investigations to protect individuals' health during product use.

Regioselective amination of 4-methylene-5,7-dinitroquinazoline: a mechanistic consideration on non-conventional N-H—π interactions between amine and ethylene moiety

ABSTRACT Pi (π) interactions originating from the N-H bond of amine and ethylene moiety have been explored on the mechanism of aromatic nucleophilic substitution (ArSN) of the nitro group of 4-methylene-5,7-dinitroquinazoline with methylamine in the gas phase and solvent media within DFT framework. The free energy profiles confirmed that the amination should take place at peri-position and calculations support the one-step mechanism through a transition state with no intermediate in the reaction route. Stabilisation of peri-transition state by intramolecular weak interaction akin to hydrogen bonding N-H—CH2 = C leads to the regioselective amination at peri-position of 4-methylene-5,7-dinitroquinazoline. The intramolecular hydrogen bond interactions at N-H—CH2 = C in the peri-transition state are strongly supported by a red shift in N-H stretching vibrations in simulated IR spectra and are confirmed by studying energetics of amination of structural/electronic analogues of 4-methylene-5,7-dinitroquinazoline. The present study established that ethylene plays an important role as an efficient H-bond acceptor in fixing the regioselectivity at peri-position in the amination of 4-methylene-5,7-dinitroquinazoline. This is the first-ever report for the exploration of the role of ethylene moiety as a hydrogen bond acceptor in mediating the regioselectivity of organic reactions.

Pharmacophore-based virtual screening of bioactive peptides as dipeptidyl peptidase 4 inhibitor for type 2 diabetes mellitus drug candidates

Background: Diabetes is a chronic disease characterised by high blood sugar levels. Glucose that accumulates in the blood without being properly absorbed by the body's cells can cause various organ problems. If diabetes is not properly controlled, various complications can occur that endanger the life of the affected person. Objective: To find bioactive peptides that have the potential to inhibit di-peptidyl peptidase 4 (DPP-4) enzyme as anti-diabetes drug candidates. Method: This research was carried out using pharmacophore-based virtual screening. Result: The validation of the pharmacophore-based virtual screening method showed that model III, which had five pharmacophore features consisting of three Pi interactions, one hydrogen bond donor, and three hydrogen acceptors, was the best pharmacophore model with the values of AUC 0.59; EF 1.2; Se 0.69; Sp 0.94; ACC 0.84; Ya 0.06; and GH 0.2. The screening of the 168,400 short-chain peptides using validated pharmacophore model III gave 51 tetrapeptides as the hits compounds with a pharmacophore fit score of more than 50.0%. Conclusion: In total, 51 tetrapeptides were enlisted as potential as anti-diabetes mellitus drug candidates.

Design, synthesis, and molecular docking of new phenothiazine incorporated N-Mannich bases as promising antimicrobial agents

The present work aims to synthesize four series of phenothiazine incorporation Mannich bases. Therefore, 10-methyl-10H-phenothiazine-3-sulfonamide (4) which was subjected to react with some secondary amines and formaldehyde to give the Mannich bases 5a-f, and 6–13. Compound 13 was then subjected to react with some secondary amines and formaldehyde to give the corresponding Mannich bases 14a-f. In total, twenty-two new compounds were synthesized and evaluated for in vitro growth inhibition activity against P. aeruginosa, E. coli, and S. aureus. Among the tested compounds, compounds 3, 5a, 5c, 6, 12, 13, 14d, and 14e exhibited good activity with a MIC value (12.5 μg/mL), compounds 5b, 10, 11, 14a, and 14c exhibited strong activity against the growth of S. aureus with a MIC value (6.25 μg/mL), and compound 14b superior against S. aureus with a MIC value (3.125 μg/mL) compared to drug reference ciprofloxacin with MIC value (2 μg/mL). The molecular docking investigation revealed the presence of many derivatives with high binding affinities and distinct interaction patterns with the target protein. Derivatives 14a-e emerged as the most promising possibilities, displaying the greatest binding energies and a varied variety of interaction types, including hydrogen bonding and pi interactions, over different distances, with derivative 14b exhibiting the highest binding energy at S = −8.3093 kcal/mol. These derivatives displayed superior binding affinities and various interaction mechanisms with the target protein, suggesting that they have great promise as lead compounds for future development into therapeutic medicines.

Identification of Novel Bisamide-Decorated Benzotriazole Derivatives as Anti-Phytopathogenic Virus Agents: Bioactivity Evaluation and Computational Simulation.

As a notorious phytopathogenic virus, the tobacco mosaic virus (TMV) severely reduced the quality of crops worldwide and caused critical constraints on agricultural production. The development of novel virucides is a persuasive strategy to address this predicament. Herein, a series of novel bisamide-decorated benzotriazole derivatives were elaborately prepared and screened. Biological tests implied that the optimized compound 7d possessed the most brilliant antiviral inactive profile (EC50 = 157.6 μg/mL) and apparently surpassed that of commercial ribavirin (EC50 = 442.1 μg/mL) 2.8-fold. The preliminary antiviral mechanism was elaborately investigated via transmission electron microscopy, microscale thermophoresis (MST) determination, RT-qPCR, and Western blot analysis. The results showed that compound 7d blocked the assembly of TMV by binding with coat protein (Kd = 0.7 μM) and suppressed TMV coat protein gene expression and biosynthesis process. Computational simulations indicated that 7d displayed strong H-bonds and pi interactions with TMV coat protein, affording a lower binding energy (ΔGbind = -17.8 kcal/mol) compared with Ribavirin (ΔGbind = -10.7 kcal/mol). Overall, current results present a valuable perception of bisamide decorated benzotriazole derivatives with appreciably virustatic competence and should be profoundly developed as virucidal candidates in agrochemical.

In vitro and in silico studies reveal antidiabetic properties of arylbenzofurans from the root bark of Morus mesozygia Stapf.

Diabetes remains an important disease worldwide with about 500 million patients globally. In tropical Africa, Morus mesozygia is traditionally used in the treatment of diabetes. Biological and phytochemical investigation of the root bark extracts of the plant led to the isolation of a new prenylated arylbenzofuran named 7-(3-hydroxy-3-methylbutyl)moracin M (1) and two congeners, moracins P (2) and M (3). When compared to acarbose (IC50 = 486µM), all the isolated compounds are better inhibitors of α-glucosidase with in vitro IC50 values of 16.9, 16.6, and 40.9 µM, respectively. However, they were not active against α-amylase. The compounds also demonstrated moderate inhibition of dipeptidyl peptidase-4 (DPP4). Based on in silico docking studies, all isolates (1, 2, and 3) exhibit binding affinities of -8.7, -9.5, and -8.5kcal/mol, respectively against α-glucosidase enzyme (PDB: 3AJ7). They are stabilized within the α-glucosidase active site through hydrogen bonds, pi interactions, and hydrophobic interactions. This study provides scientific support for the traditional use of Morus mesozygia in the treatment of diabetes as well as adding to the repository of α-glucosidase inhibitory agents.

Green synthesis, in silico modeling, and biological evaluation of N-substituted (Z)-5-arylidene imidazolidine/thiazolidine-2,4-dione/4-thione derivatives catalyzed by Bu SO3H core-shell nanostructures.

In this effort, the immobilization of guanidine-sulfonate on the surface of Fe3O4 MNPs (magnetic nanoparticles) as a novel acid nanocatalyst has been successfully reported for the synthesis of N-substituted (Z)-5-arylidene thiazolidine-2,4-dione and related cyclic derivatives, including rhodanine (RHD) and hydantoin (HYD) via a one-pot multiple-component reaction under green conditions. The products were characterized by SEM, TEM, TGA, EDS, BET techniques, VSM, and FTIR. The novel compounds synthesized using this methodology, designated as series La (1-9), Lb (1-8), and Lc (1-8), were subjected to anticancer screening against A549 and MCF7cell lines via MTT assays. Notably, several compounds (L1a, L2a, L3a, L1b, L2b, L3b, and L4b) exhibited potent antiproliferative activities, with observed IC50 values as low as 1.23 μM and 1.02 μM against MCF-7 cells, thereby outperforming the established anticancer drugs doxorubicin and cisplatin. Molecular docking and dynamics simulations revealed that ligands L1a, L2a, and L3a strongly interact with the protein target 3CD8, with L1a displaying significant hydrophobic and hydrogen bonding interactions and L2a engaging in unique pi-pi stacking with key residues. For protein 2WGJ, ligand L4b exhibited exceptional binding affinity, characterized by robust hydrogen bonding, hydrophobic interactions, and additional stabilizing mechanisms such as water bridges and pi interactions. Hence, N-substituted (Z)-5-arylidene thiazolidine-2,4-dione and its cyclic derivatives may serve as promising candidates for further exploration in the development of new multi-target cancer chemotherapy agents. These findings introduce promising anticancer agents and establish Fe3O4 MNPs as a versatile and environmentally sustainable catalytic platform in drug discovery.

The potential of selenium to induce salt stress tolerance in Brassica rapa: Evaluation of biochemical, physiological and molecular phenomenon

The efficacy of selenium (Se) to ameliorate salinity stress in Brassica rapa was elucidated using an in-vitro and in-silico hybrid approach. Selenium was applied as a seed priming agent on the seeds grown in salt-spiked soils. The priming treatment facilitated all the growth indicators and physiological parameters, including chlorophyll synthesis, sugar contents, gas exchange attributes, etc. The advantageous effects of Se were accredited to the alleviation of salinity stress through reducing the malondialdehyde (MDA), proline, electrolyte leakage, and hydrogen peroxide (H2O2) level. Similarly, modulations in the expression of genes encoding antioxidative enzymes enhanced reactive oxygen species (ROS) scavenging capacity along with a decrease in sodium (Na+) ions, reciprocally enhancing potassium (K+) ions and resulting in a higher K+/Na+ ratio. Additionally, based on in silico studies, a significant difference in the surface overlap of the stress-responsive proteins, including DREB, SOS3, and STXBP1 of B. rapa, was observed, indicating the involvement of Se in the foiling interaction of NaCl with the enzymes. In the case of the CAT macromolecule, ligands NaCl exhibited a -1.9-fold lower docking score as compared to sodium selenite -4.9-fold, indicating a more overlapped interactive surface than sodium chloride. The binding energies analysis recorded -3.3 kcal/mol of binding energy for the best pose of sodium selenite in the case of DREB, while it was -3.5 and -3.5 kcal.mol-1 for SOS3 and 1 STXBP1, respectively. Ligand analysis revealed a frequent existence of hydrogen bonds besides the hydrophobic interactions, salt bridges, and pi–pi interactions representing high structural and functional stability. Results of the current study unveiled an in-vitro and in-silico hybrid bioinformatics system to unveil the biochemical, physiological and molecular phenomenon behind selenium-driven salt resilience in B. rapa.

Finding small molecular compounds to decrease trimethylamine oxide levels in atherosclerosis by virtual screening

Abstract The intestinal microbial metabolite trimethylamine oxide (TMAO) affects the formation and development of atherosclerosis (AS). The design and development of an effective targeted drug to reduce serum TMAO levels may provide new avenues for inhibiting AS morbidity. Target genes that may elevate TMAO levels in patients with AS were explored using bioinformatics, virtual screening, and molecular dynamics (MD). We expected these genes to indicate potential TMAO inhibitors. Of these genes, hFMO3 was responsible for increasing TMAO levels. Four small-molecule compounds (SMC-1, SMC-2, SMC-3, and SMC-4) with the lowest binding energy and CGenFF penalty < 10 were connected to the main binding pocket of hFMO3 by hydrogen and/or cation–pi interactions. A 100 ns MD simulation showed that the four systems quickly reached equilibrium. The root mean square deviation of all four small-molecule compounds was less than 0.35 nm, that of the four ligand complexes was less than 0.40 nm, and the average deviations of each amino acid residue from the reference position over time did not differ. Molecular mechanics Poisson–Boltzmann surface area analyses showed that SMC-2, SMC-3, and SMC-4 bound very well to hFMO3, and the energy contribution of the key residues LEU40 and GLU32 was more remarkable in SMC-2, SMC-3, and SMC-4. These four small-molecule compounds may be useful as targeted drugs to reduce serum TMAO levels, inhibiting atherosclerosis formation.

Elucidation of benzene sulfonamide derivative binding at a novel interprotomer pocket of wild type and mutants of coxsackievirus B3 viral capsid using molecular dynamics simulations and density functional theory

Coxsackievirus B3 (CVB3), a serotype of enterovirus B, causes hand, foot, and mouth disease; pericarditis; and myocarditis. A benzene sulfonamide derivative is reported to have inhibitory activity against wild-type (WT) and eight mutants of the viral capsid of CVB3. Furthermore, the crystal structure of the complex formed between WT viral capsid of CVB3 and the derivative revealed binding at a novel druggable interprotomer pocket. We investigated how the compound could be a potent inhibitor of both WT and some mutants of CVB3 by determining binding to the viral capsid and the interaction energy with the binding pocket based on molecular dynamics simulations and density functional theory. We found that hydrogen bonds, pi–pi interactions, and electrostatic interactions are the key interactions with a protomer unit of CVB3 viral capsid. The residual interaction energy determined using density functional theory revealed key binding with VP1:Arg234 and a residue in the nearby VP1 unit (VP1’:Arg219). These results explain why the compound is still a potent inhibitor against eight mutants. Moreover, the decreased inhibitory activity for some mutants could be explained by the calculated binding energy and the highest occupied molecular orbital and lowest unoccupied molecular orbital energy. The results will be helpful for the development of drugs resistant to CVB3.

Photochromism of two 1D coordination polymers constructed by two ligands of 1-carboxyethyl-4,4′-bipyridinium and N,N′-bis(carboxyethyl)-4,4′-bipyridinium

In this paper, two one-dimensional (1D) coordination polymers were designed and prepared by 1-carboxyethyl-4,4′-bipyridinium (CEbpy) and N,N′-bis(carboxyethyl)-4,4′-bipyridinium (BCEbpy) ligands, i.e. {[Cu0.5(CEbpy)]·(1,2,4-H2BTC)·H2O}n (1) and {[Mn0.5(CEbpy)(H2O)]·[Mn(1,2,4-BTC)(H2O)5]·0.5(BCEbpy)·DMF·4H2O}n (2), indicating superior photochromic behavior and photoresponse properties. The crystal structures and electronic transport behaviors of two compounds were studied. Single crystal X-ray analyses reveal that compounds 1 and 2 crystallize in the triclinic space group P-1. Compound 1 exhibits intramolecular electron transport, whereas compound 2 exhibits both intramolecular and intermolecular electron transport, with a photo-response sequence that is 1 less than 2. The non-covalent interactions were investigated by the DFT method, demonstrating pi−pi interactions greatly promote the photoresponsive electron transfer for compounds 1 and 2.

Delineating Structural Propensities of the 4E-BP2 Protein via Integrative Modeling and Clustering.

The intrinsically disordered 4E-BP2 protein regulates mRNA cap-dependent translation through interaction with the predominantly folded eukaryotic initiation factor 4E (eIF4E). Phosphorylation of 4E-BP2 dramatically reduces the level of eIF4E binding, in part by stabilizing a binding-incompatible folded domain. Here, we used a Rosetta-based sampling algorithm optimized for IDRs to generate initial ensembles for two phospho forms of 4E-BP2, non- and 5-fold phosphorylated (NP and 5P, respectively), with the 5P folded domain flanked by N- and C-terminal IDRs (N-IDR and C-IDR, respectively). We then applied an integrative Bayesian approach to obtain NP and 5P conformational ensembles that agree with experimental data from nuclear magnetic resonance, small-angle X-ray scattering, and single-molecule Förster resonance energy transfer (smFRET). For the NP state, inter-residue distance scaling and 2D maps revealed the role of charge segregation and pi interactions in driving contacts between distal regions of the chain (∼70 residues apart). The 5P ensemble shows prominent contacts of the N-IDR region with the two phosphosites in the folded domain, pT37 and pT46, and, to a lesser extent, delocalized interactions with the C-IDR region. Agglomerative hierarchical clustering led to partitioning of each of the two ensembles into four clusters with different global dimensions and contact maps. This helped delineate an NP cluster that, based on our smFRET data, is compatible with the eIF4E-bound state. 5P clusters were differentiated by interactions of C-IDR with the folded domain and of the N-IDR with the two phosphosites in the folded domain. Our study provides both a better visualization of fundamental structural poses of 4E-BP2 and a set of falsifiable insights on intrachain interactions that bias folding and binding of this protein.

Tomatidine Extraction from Various Solvents and Cancer Inhibition Mechanism Through In Silico Analysis

Tomatidine is an alkaloid-steroid contained in tomato plant organs that potentially developed as an anti-cancer molecule. However, inappropriate use of solvents is frequently becoming an obstacle in the extractions process. In addition, the mechanism of action of tomatidine in the inhibition of cancer cell signaling pathways needs to be investigated. Therefore, this research aims to discover an appropriate solvent to extract tomatidine effectively, and to analyze the inhibition mechanism of tomatidine against the cancer growth pathway. A total of 80 kg of fresh tomatoes were cut into pieces and steamed at 120 °C for 30 min, then mashed and soaked for 3 days in 70 % ethanol, aquadest, petroleum ether, and chloroform separately, continued with GC/MS analysis. Molecular docking was conducted using targeted proteins including B-Raf proto-oncogen serine/ threonine protein kinase (BRAF), Vascular endothelial growth factor A (VEGFA), Smoothened protein (SMO), Cyclin-dependent kinase 2 (CDK2), and Tyrosine-protein kinase/ Janus kinase-1 (JAK1). The ligand-receptor was performed using AutoDock Vina v1.2.0. The highest extracted tomatidine was found in chloroform at 2.44 % of total alkaloid-steroid, and cannot be found in water. The highest interaction is observed in the SMO-tomatidine interaction complex, followed by JAK-1. Furthermore, physicochemical properties of tomatidine make it invaginated into the hydrophobic side of the target proteins that are mainly triggered by van der Waals and alkyl interaction. Based on the in-silico study, tomatidine significantly interacted in the oncogenic signaling pathways that therapeutically potential inhibit cancer cell proliferation. Further study should be focused on the effectiveness analysis of the SHH signaling pathway in the cancer cell. HIGHLIGHTS Important findings in this study include: Tomatidine, an alkaloid-steroid, is properly extracted in chloroform, petroleum ether and 70 % ethanol, however cannot extracted in aquadest. Furthermore, the aquadest content in 70 % ethanol is likely to reduce the solubility of the tomatidine The tomatidine physicochemical property provides a closed covalent bond that makes it more insoluble in the polar solvent. The only polar side is supported by the hydroxyl group in C-4, side chain C-17, and amide side in N-24 that allowed hydrogen bond formation which is relevant to the docking result In molecular docking, tomatidine strongly triggers Van der Waal forces, alkyl, and pi interaction than hydrogen bond or ionic force Interestingly, ligand-receptor interaction always makes tomatidine invaginated or folded into the protein hydrophobic side and strongly attract non-polar and aromatic amino acid, mostly Val, Ala, Leu, and Phe The significant finding is that tomatidine creates valid interactions with CDK2, BRAF, VEGFA, JAK1, and SMO that are involved in cancer cell proliferation, evading apoptosis, and sustained angiogenesis. The highest interaction is observed in the SMO-tomatidine interaction complex, which may affect the Sonic Hedgehog (SHH) signaling pathway (one of the most significant oncogenic pathways in various types of cancer) Tomatidine is therapeutically potential to inhibit cancer cell proliferation through protein inhibition activities against the SHH signaling pathway in the cancer cell GRAPHICAL ABSTRACT

Binding characteristics and conformational changes in alpha-2-macroglobulin by the dietary flavanone naringenin: biophysical and computational approach

In the present study, we investigated the interaction of alpha-2-macroglobulin (α2M) with naringenin using multi-spectroscopic, molecular docking, and molecular simulation approaches to identify the functional changes and structural variations in the α2M structure. Our study suggests that naringenin compromised α2M anti-proteinase activity. The results of absorption spectroscopy and fluorescence measurement showed that naringenin-α2M formed a complex with a binding constant of (kb)∼104, indicative of moderate binding. The value of ΔG° in the binding indicates the process to be spontaneous and the major force responsible to be hydrophobic interaction. The findings of FRET reveal the binding distance between naringenin and the amino acids of α2M was 2.82 nm. The secondary structural analysis of α2M with naringenin using multi-spectroscopic methods like synchronous fluorescence, red-edge excitation shift (REES), FTIR, and CD spectra further confirmed the significant conformational alterations in the protein. Molecular docking approach reveals the interactions between naringenin and α2M to be hydrogen bonds, van der Waals forces, and pi interactions, which considerably favour and stabilise the binding. Molecular dynamics modelling simulations also supported the steady binding with the least RMSD deviations. Our study suggests that naringenin interacts with α2M to alter its confirmation and compromise its activity. Communicated by Ramaswamy H. Sarma

Treatment of atrazine-containing wastewater by algae-bacteria consortia: Signal transmission and metabolic mechanism

Atrazine is a toxic endocrine disruptor. Biological treatment methods are considered to be effective. In the present study, a modified version of the algae-bacteria consortia (ABC) was established and a control was simultaneously set up to investigate the synergistic relationship between bacteria and algae and the mechanism by which atrazine is metabolized by those microorganisms. The total nitrogen (TN) removal efficiency of the ABC reached 89.24% and the atrazine concentration was reduced to below the level recommended by the Environment Protection Agency (EPA) regulatory standards within 25 days. The protein signal released from the extracellular polymeric substances (EPS) secreted by the microorganisms triggered the resistance mechanism of the algae, and the conversion of humic acid to fulvic acid and electron transfer constituted the synergistic mechanism between the bacteria and algae. The mechanism by which atrazine is metabolized by the ABC mainly consists of hydrogen bonding, H–pi interactions, and cation exchange with atzA for hydrolysis, followed by a reaction with atzC for decomposition to non-toxic cyanuric acid. Proteobacteria was the dominant phylum for bacterial community evolution under atrazine stress, and the analysis revealed that the removal of atrazine within the ABC was mainly dependent on the proportion of Proteobacteria and the expression of degradation genes (p < 0.01). EPS played a major role in the removal of atrazine within the single bacteria group (p < 0.01).

Ring-and-Lock Interactions in Self-Healable Styrenic Copolymers.

Commodity copolymers offer many useful applications, and their durability is critical in maintaining desired functions and retaining sustainability. These studies show that primarily alternating styrene/n-butyl acrylate [p(Sty/nBA)] copolymers self-heal without external intervention when monomer molar ratios are within the 45:55-53:47 range. This behavior is attributed to the favorable interchain interactions between aliphatic nBA side groups being sandwiched by aromatic rings forming ring-and-lock associations driven by pi-sigma-pi (π-σ-π) interactions. Guided by molecular dynamics (MD) simulations combined with spectroscopic and thermomechanical analysis, the ring-and-lock interchain van der Waals forces between π orbitals of aromatic rings and sigma components of aliphatic side groups are responsible for self-healing. Despite the frequent occurrence of these interactions in biological systems (proteins, nucleic acids, lipids, and polysaccharides), these largely unexplored weak and ubiquitous molecular forces between the soft acid aliphatic and soft base aromatic electrons may be valuable assets in the development of polymeric materials with sustainable properties.

Identification of Natural Compounds of the Apple as Inhibitors against Cholinesterase for the Treatment of Alzheimer’s Disease: An In Silico Molecular Docking Simulation and ADMET Study

Alzheimer's disease (AD), the most common type of dementia in older people, causes neurological problems associated with memory and thinking. The key enzymes involved in Alzheimer's disease pathways are acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Because of this, there is a lot of interest in finding new AChE inhibitors. Among compounds that are not alkaloids, flavonoids have stood out as good candidates. The apple fruit, Malus domestica (Rosaceae), is second only to cranberries regarding total phenolic compound concentration. Computational tools and biological databases were used to investigate enzymes and natural compounds. Molecular docking techniques were used to analyze the interactions of natural compounds of the apple with enzymes involved in the central nervous system (CNS), acetylcholinesterase, and butyrylcholinesterase, followed by binding affinity calculations using the AutoDock tool. The molecular docking results revealed that CID: 107905 exhibited the best interactions with AChE, with a binding affinity of -12.2 kcal/mol, and CID: 163103561 showed the highest binding affinity with BuChE, i.e., -11.2 kcal/mol. Importantly, it was observed that amino acid residue Trp286 of AChE was involved in hydrogen bond formation, Van Der Walls interactions, and Pi-Sigma/Pi-Pi interactions in the studied complexes. Moreover, the results of the Molecular Dynamics Simulation (MDS) analysis indicated interaction stability. This study shows that CID: 12000657 could be used as an AChE inhibitor and CID: 135398658 as a BuChE inhibitor to treat Alzheimer's disease and other neurological disorders.