Thiazolidine-2,4-dione derivatives as potential α-glucosidase inhibitors: Synthesis, inhibitory activity, binding interaction and hypoglycemic activity.

In order to find effective α-glucosidase inhibitors, a series of thiazolidine-2,4-dione derivatives (C1 âˆ¼ 36) were synthesized and evaluated for α-glucosidase inhibitory activity. Compared to positive control acarbose (IC50 = 654.35 ± 65.81 µM), all compounds (C1 âˆ¼ 36) showed stronger α-glucosidase inhibitory activity with IC50 values of 0.52 ± 0.06 âˆ¼ 9.31 ± 0.96 µM. Among them, C23 with the best anti-α-glucosidase activity was a reversible mixed-type inhibitor. Fluorescence quenching suggested the binding process of C23 with α-glucosidase in a static process. Fluorescence quenching, CD spectra, and 3D fluorescence spectra results also implied that the binding of C23 with α-glucosidase caused the conformational change of α-glucosidase to inhibit the activity. Molecular docking displayed the binding interaction of C23 with α-glucosidase. Compound C23 (8 âˆ¼ 64 µM) showed no cytotoxicity against LO2 and 293 cells. Moreover, oral administration of C23 (50 mg/kg) could reduce blood glucose and improve glucose tolerance in mice.

Human serum albumin subdomain IB is physiologically adapted for payloading homopterocarpin to human aldehyde dehydrogenase: Combinatorial in vitro and in silico approaches.

The in vitro interactions of homopterocarpin, a potent antioxidant and anti-ulcerative isoflavonoid, with human serum albumin (HSA) and human aldehyde dehydrogenase (hALDH) were explored using various spectroscopic methods, in silico and molecular dynamic (MD) studies. The result showed that homopterocarpin quenched the intrinsic fluorescences of HSA and hALDH. The interactions were entropically favorable, driven primarily by hydrophobic interactions. The proteins have one binding site for the isoflavonoid. This interaction  increased the proteins hydrodynamic radii by over 5% and caused a slight change in HSA surface hydrophobicity Homopterocarpin preferentially binds to HSA subdomain IB with a binding affinity of -10.1 kcal/mol before interaction stoke with hALDH (-8.4 kcal/mol). HSA-homopterocarpin complex attained pharmacokinetic-pharmacodynamics reversible equilibration time faster than ALDH-homopterocarpin. However, the probable and eventual therapeutic effect of homopterocarpin is the mixed inhibition ALDH activity having a Ki value of 20.74 µM. The MD results revealed the stabilization of the complex in HSA-homopterocarpin and ALDH-homopterocarpin from their respective spatial structures of the complex. The findings of this research will provide significant benefits in understanding the pharmacokinetics characteristics of homopterocarpin at the clinical level.

Advance in dietary polyphenols as dipeptidyl peptidase-IV inhibitors to alleviate type 2 diabetes mellitus: aspects from structure-activity relationship and characterization methods.

Dietary polyphenols with great antidiabetic effects are the most abundant components in edible products. Dietary polyphenols have attracted attention as dipeptidyl peptidase-IV (DPP-IV) inhibitors and indirectly improve insulin secretion. The DPP-IV inhibitory activities of dietary polyphenols depend on their structural diversity. Screening methods that can be used to rapidly and accurately identify potential polyphenol DPP-IV inhibitors are urgently needed. This review focuses on the relationship between the structures of dietary polyphenols and their DPP-IV inhibitory effects. Different characterization methods used for polyphenols as DPP-IV inhibitors have been summarized and compared. We conclude that the position and number of hydroxyl groups, methoxy groups, glycosylated groups, and the extent of conjugation influence the efficiency of inhibition of DPP-IV. Various combinations of methods, such as in-vitro enzymatic inhibition, ex-vivo/in-vivo enzymatic inhibition, cell-based in situ, and in-silico virtual screening, are used to evaluate the DPP-IV inhibitory effects of dietary polyphenols. Further investigations of polyphenol DPP-IV inhibitors will improve the bioaccessibility and bioavailability of these bioactive compounds. Exploration of (i) dietary polyphenols derived from multiple targets, that can prevent diabetes, and (ii) actual binding interactions via multispectral analysis, to understand the binding interactions in the complexes, is required.

Assessment of the Binding of Pseudallecin A to Human Serum Albumin with Multi-Spectroscopic Analysis, Molecular Docking and Molecular Dynamic Simulation.

The binding of pseudallecin A (PA), a potential antibiotic with strong inhibitory activities against Gram-positive Escherichia coli and Gram-negative Staphylococcus aureus, to human serum albumin (HSA) was explored. The interaction between them was assessed by multi-spectroscopic analysis, binding site competitive analysis, molecular docking and molecular dynamic simulation, showing the results as follows: PA effectively quenched the innate fluorescence of HSA by a static quenching process, formed a complex at a molar ratio of approximately 1 : 1 and performed an effective non-radiative energy transfer; the binding of PA to HSA was a spontaneous exothermic reaction driven by enthalpy with strong affinity and had a slight effect on the conformation of HSA; PA bound at site III of HSA and hydrogen bonds were the major binding forces to maintain the stability of the PA-HSA complex. Molecular dynamic simulation was performed to calculate the root mean square deviation (RMSD), root mean square fluctuation (RMSF) and radius of gyration (Rg) for this complex and effectively supported the spectroscopic outcome. These results meant that the delivery and distribution of PA as a water-insoluble molecule can be efficiently accomplished via HSA in human blood and, it has a good potential for future drug application and pharmacological development.

Identification of Potential p38γ Inhibitors via In Silico Screening, In Vitro Bioassay and Molecular Dynamics Simulation Studies.

Protein kinase p38γ is an attractive target against cancer because it plays a pivotal role in cancer cell proliferation by phosphorylating the retinoblastoma tumour suppressor protein. Therefore, inhibition of p38γ with active small molecules represents an attractive alternative for developing anti-cancer drugs. In this work, we present a rigorous and systematic virtual screening framework to identify potential p38γ inhibitors against cancer. We combined the use of machine learning-based quantitative structure activity relationship modelling with conventional computer-aided drug discovery techniques, namely molecular docking and ligand-based methods, to identify potential p38γ inhibitors. The hit compounds were filtered using negative design techniques and then assessed for their binding stability with p38γ through molecular dynamics simulations. To this end, we identified a promising compound that inhibits p38γ activity at nanomolar concentrations and hepatocellular carcinoma cell growth in vitro in the low micromolar range. This hit compound could serve as a potential scaffold for further development of a potent p38γ inhibitor against cancer.

Catalytic, Theoretical, and Biological Investigations of Ternary Metal (II) Complexes Derived from L-Valine-Based Schiff Bases and Heterocyclic Bases.

A new series of ternary metal complexes, including Co(II), Ni(II), Cu(II), and Zn(II), were synthesized and characterized by elemental analysis and diverse spectroscopic methods. The complexes were synthesized from respective metal salts with Schiff's-base-containing amino acids, salicylaldehyde derivatives, and heterocyclic bases. The amino acids containing Schiff bases showed promising pharmacological properties upon complexation. Based on satisfactory elemental analyses and various spectroscopic techniques, these complexes revealed a distorted, square pyramidal geometry around metal ions. The molecular structures of the complexes were optimized by DFT calculations. Quantum calculations were performed with the density functional method for which the LACVP++ basis set was used to find the optimized molecular structure of the complexes. The metal complexes were subjected to an electrochemical investigation to determine the redox behavior and oxidation state of the metal ions. Furthermore, all complexes were utilized for catalytic assets of a multi-component Mannich reaction for the preparation of -amino carbonyl derivatives. The synthesized complexes were tested to determine their antibacterial activity against E. coli, K. pneumoniae, and S. aureus bacteria. To evaluate the cytotoxic effects of the Cu(II) complexes, lung cancer (A549), cervical cancer (HeLa), and breast cancer (MCF-7) cells compared to normal cells, cell lines such as human dermal fibroblasts (HDF) were used. Further, the docking study parameters were supported, for which it was observed that the metal complexes could be effective in anticancer applications.

DNA Binding and Cleavage, Stopped-Flow Kinetic, Mechanistic, and Molecular Docking Studies of Cationic Ruthenium(II) Nitrosyl Complexes Containing "NS4" Core.

This work aimed to evaluate in vitro DNA binding mechanistically of cationic nitrosyl ruthenium complex [RuNOTSP]+ and its ligand (TSPH2) in detail, correlate the findings with cleavage activity, and draw conclusions about the impact of the metal center. Theoretical studies were performed for [RuNOTSP]+, TSPH2, and its anion TSP-2 using DFT/B3LYP theory to calculate optimized energy, binding energy, and chemical reactivity. Since nearly all medications function by attaching to a particular protein or DNA, the in vitro calf thymus DNA (ctDNA) binding studies of [RuNOTSP]+ and TSPH2 with ctDNA were examined mechanistically using a variety of biophysical techniques. Fluorescence experiments showed that both compounds effectively bind to ctDNA through intercalative/electrostatic interactions via the DNA helix's phosphate backbone. The intrinsic binding constants (Kb), (2.4 ± 0.2) × 105 M-1 ([RuNOTSP]+) and (1.9 ± 0.3) × 105 M-1 (TSPH2), as well as the enhancement dynamic constants (KD), (3.3 ± 0.3) × 104 M-1 ([RuNOTSP]+) and (2.6 ± 0.2) × 104 M-1 (TSPH2), reveal that [RuNOTSP]+ has a greater binding propensity for DNA compared to TSPH2. Stopped-flow investigations showed that both [RuNOTSP]+ and TSPH2 bind through two reversible steps: a fast second-order binding, followed by a slow first-order isomerization reaction via a static quenching mechanism. For the first and second steps of [RuNOTSP]+ and TSPH2, the detailed binding parameters were established. The total binding constants for [RuNOTSP]+ (Ka = 43.7 M-1, Kd = 2.3 × 10-2 M-1, ΔG0 = -36.6 kJ mol-1) and TSPH2 (Ka = 15.1 M-1, Kd = 66 × 10-2 M, ΔG0 = -19 kJ mol-1) revealed that the relative reactivity is approximately ([RuNOTSP]+)/(TSPH2) = 3/1. The significantly negative ΔG0 values are consistent with a spontaneous binding reaction to both [RuNOTSP]+ and TSPH2, with the former being very favorable. The findings showed that the Ru(II) center had an effect on the reaction rate but not on the mechanism and that the cationic [RuNOTSP]+ was a more highly effective DNA binder than the ligand TSPH2 via strong electrostatic interaction with the phosphate end of DNA. Because of its higher DNA binding affinity, cationic [RuNOTSP]+ demonstrated higher cleavage efficiency towards the minor groove of pBR322 DNA via the hydrolytic pathway than TSPH2, revealing the synergy effect of TSPH2 in the form of the complex. Furthermore, the mode of interaction of both compounds with ctDNA has also been supported by molecular docking.

Influence of milk fat on the physicochemical property of nanoencapsulated curcumin and enhancement of its biological properties thereof.

Curcumin, bioactive from turmeric Curcuma longa, has been known for its therapeutic properties. However, its lipophilic nature and poor bioavailability are the constraints to harnessing its properties. Encapsulation in nano-size helps to alleviate the constraints and enhance its biological properties due to its higher surface area. The study aims to encapsulate curcumin in a nanometer size range by solubilizing in lipid (milk fat) and using milk protein as a water-soluble carrier. The lipid:curcumin ratio (1:0.05, 1:0.1, 1:0.2, 1.5:0.1, 1.5:0.2, 2.0:0.1 and 2:0.2% (w/w)) produced nanoemulsion with droplets sizes 30-200 nm. The sample containing lipid: curcumin, as 1.0:0.05 resulted in an encapsulation efficiency of 92.6%, and its binding interaction with the carrier, was KD = 4.7 µM. A high solubility of curcumin in milk fat and digestion during in vitro lipolysis increased its bioaccessibility. A simulated gastro-intestinal in vitro studies showed that cumulative release percentage of nanoencapsulated curcumin was 60% at pH 7.4 compared to 0.8% of native curcumin. The anti-microbial property of nanoencapsulated curcumin was more potent than native curcumin against food pathogenic organisms such as S. aureus, B. cereus, E. coli, B. subtilis, P. aeruginosa, P. aeruginosa, C. violaceum. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05684-5.

Bisphenol A Analogs Induce Cellular Dysfunction in Human Trophoblast Cells in a Thyroid Hormone Receptor-Dependent Manner: In Silico and In Vitro Analyses.

Bisphenol A (BPA) and its analogs are frequently detected in human daily necessities and environmental media. Placental thyroid hormone plays an important role in fetal development. Herein, we followed the adverse outcome pathway (AOP) to explore the toxic mechanisms of BPA and its analogs toward placental thyroid hormone receptor (TR). First, the TOX21 database was used, and the interactions between BPA analogs and the ligand-binding domains (LBDs) of two subtypes of TR (TRα and TRß) were subjected to in silico screening using molecular docking (MD) and molecular dynamics simulation (MDS). Fluorescence spectra and circular dichroism (CD) showed that BPA and its analogs interfere with TRs as a molecular initiation event (MIE), including static fluorescence quenching and secondary structural content changes in TR-LBDs. Key events (KEs) of the AOP, including the toxicity induced in placental chorionic trophoblast cells (HTR-8/SVneo) by an inverted U-shaped dose effect and changes in ROS levels, were tested in vitro. BPA, BPB, and BPAF significantly changed the expression level of TRß, and only BPAF significantly downregulated the expression level of TRα. In conclusion, our study contributes to the health risk assessment of BPA and its analogs regarding placental adverse outcomes (AOs).

Application of a novel fluorescence intensity assay: identification of distinct fatty acetates as volatile compounds that bind specifically to amino acid region 149-168 of a transmembrane receptor CD36.

The cluster of differentiation 36 (CD36) is a transmembrane receptor expressed in various cells and has diverse lipid ligands. The expression of CD36 in the murine olfactory epithelium and its ability to recognize certain species of fatty aldehydes, a class of odor-active volatile compounds, have suggested a role for this receptor in the capture of specific odorants in the nasal cavity of mammals. However, the spectrum of CD36-recognizable volatile compounds is poorly understood. In this study, we employed our recently devised assay with fluorescently labeled peptides as probes (fluorescence intensity assay) and identified distinct fatty acetates as volatile compounds that bind specifically to amino acid region 149-168 of CD36 (eg dodecyl and tetradecyl acetates). The present findings demonstrate the utility of our assay for the discovery of novel CD36 ligands and support the notion that the receptor functions as a captor of volatile compounds in the mammalian olfactory system.

Interaction Characterization of a Tyrosine Kinase Inhibitor Erlotinib with a Model Transport Protein in the Presence of Quercetin: A Drug-Protein and Drug-Drug Interaction Investigation Using Multi-Spectroscopic and Computational Approaches.

The interaction between erlotinib (ERL) and bovine serum albumin (BSA) was studied in the presence of quercetin (QUR), a flavonoid with antioxidant properties. Ligands bind to the transport protein BSA resulting in competition between different ligands and displacing a bound ligand, resulting in higher plasma concentrations. Therefore, various spectroscopic experiments were conducted in addition to in silico studies to evaluate the interaction behavior of the BSA-ERL system in the presence and absence of QUR. The quenching curve and binding constants values suggest competition between QUR and ERL to bind to BSA. The binding constant for the BSA-ERL system decreased from 2.07 × 104 to 0.02 × 102 in the presence of QUR. The interaction of ERL with BSA at Site II is ruled out based on the site marker studies. The suggested Site on BSA for interaction with ERL is Site I. Stability of the BSA-ERL system was established with molecular dynamic simulation studies for both Site I and Site III interaction. In addition, the analysis can significantly help evaluate the effect of various quercetin-containing foods and supplements during the ERL-treatment regimen. In vitro binding evaluation provides a cheaper alternative approach to investigate ligand-protein interaction before clinical studies.

Comparative study of binding interactions between three organometallic rhodium(III) complexes with curcuminoid ligands and human serum albumin.

Organometallic rhodium(III) complexes with curcuminoid ligands attracted considerable attention in biological-related fields and the variation of curcuminoid ligands may regulate the biological activity of these organometallic rhodium(III) complexes. To deeply evaluate the biological influences of these complexes, the binding interactions between three rhodium(III) complexes with curcuminoid ligands and human serum albumin (HSA) were comparably investigated by spectroscopic and electrochemical techniques. The results suggested that the intrinsic fluorescence of HSA was quenched by three complexes through static fluorescence quenching mode. Three complexes bonded with Sudlow's site I of HSA to form ground-state compounds under the binding forces of van der Waals interactions, hydrogen bonds formation, and protonation. Finally, the native conformational structure and the thermal stability of HSA were all changed. Space steric hindrance of complexes took part in the differences of the fluorescence quenching processes, and the chemical polarity of the complexes played a vital role in the variations of the structure and biological activity of HSA. These results illustrated the molecular interactions between protein and organometallic rhodium(III) complexes with curcuminoid ligands, offering new insight about the prospective applications of analogical rhodium(III) complexes in biomedicine areas.

The interaction of folate-modified Bletilla striata polysaccharide-based micelle with bovine serum albumin.

We fabricated an amphiphilic folate-modified Bletilla striata polysaccharide (FA-BSP-SA) copolymer that exhibited good biocompatibility and superior antitumor effects. This study investigated the affinity between FA-BSP-SA and bovine serum albumin (BSA) via multispetroscopic approaches. Changes in the morphology and particle size showed that FA-BSP-SA formed a blurry "protein corona". Stern-Volmer equation demonstrated that FA-BSP-SA micelles decreased the fluorescence of BSA via static quenching. The measurement results of thermodynamic parameters (entropy change, enthalpy change, and Gibbs free energy) suggested that the binding between FA-BSP-SA and BSA was spontaneous in which Van der Waals forces and hydrogen bonding played major roles. The results from synchronous fluorescence, circular dichroism, and UV spectra also revealed that BSA conformation was slightly altered by decreasing α-helical contents. In addition, the antitumor effects in vitro of Dox@FA-BSP-SA micelles and the cellular uptake behavior of micelles in 4T1 cells were decreased after incubating with BSA.

Spectroscopic and Small-angle X-ray scattering analysis of binding between Copper(II) -1-allylimidazole complex, a potential anti-tumor agent, and bovine serum albumin.

Interactions between transport proteins and compounds with therapeutic potential are pharmacologically important. In this study, using fluorescence, circular dichroism (CD), and small-angle X-ray Scattering (SAXS), we investigated the interaction between bovine serum albumin (BSA) and a copper(II)-1-allylimidazole complex with potential anti-cancer properties. The results revealed dynamic fluorescence quenching of the model carrier protein BSA by the copper(II) complex. The enthalpy change (ΔH), free energy (ΔG), and entropy change (ΔS) were calculated to be 108 kJ/mol, -16.47 kJ/mol, and 419 J/mol K, respectively, according to the Van't Hoff equation. The reaction was an endothermic and spontaneous process, and hydrophobic interactions played a major role in binding. The results indicate a much lower affinity (Kb âˆ¼ 102-103) for the metal complex compared with similar compounds (Kb âˆ¼ 103-105). CD showed that the studied copper(II) complex does not change the secondary structure of the protein, while SAXS showed that the this compound may attach to the protein surface and stimulate interactions between proteins. The results suggest that the copper(II) complex with 1-allylimidazole binds weakly to BSA, leading to aggregation of albumin in solution, thereby altering its pharmacokinetic properties. The findings are pertinent to drug design.

Theoretical study on endocrine disrupting effects of polychlorinated dibenzo-p-dioxins using molecular docking simulation.

Polychlorinated dibenzo-p-dioxins (PCDDs) are hypothesized to exert their toxic effects in wildlife and humans via endocrine disruption. However, very scanty information is available on the underlying molecular interactions that trigger this disruption. In this study, molecular docking simulation was used to predict the susceptibility of 12 nuclear receptors to disruption via PCDD bindings. Findings revealed that androgen (AR and AR an), estrogen (ER α and ER ß), glucocorticoid (GR) and thyroid hormone (TR α and TR ß) receptors are the most probable protein targets that bind to PCDDs. Further molecular docking analyses showed that PCDD molecules mimic the modes of interaction observed for the co-crystallized ligands of the affected receptors, resulting in the formation of ligand-receptor complexes that were stabilized through electrostatic, van der Waals, pi-effect and hydrophobic interactions with 18, 17, 17, 16, 18, eight and four amino acid residues in the active sites of AR, AR an, ER α, ER ß, GR, TR α and TR ß respectively. The commonalities of these interacting amino acid residues with those utilized by dihydrotestosterone in AR, bicalutamide in AR an, 17ß-estradiol in ER α, 17ß-estradiol in ER ß, cortisol in GR, thyromimetic GC-1 in TR α and thyromimetic GC-1 in TR ß are 86%, 74%, 94%, 80%, 82%, 50% and 43% respectively. The results obtained in this study provide supporting evidence that PCDD molecules may interfere with the endocrine system via binding interactions with some vital amino acid residues in the binding pockets of AR, ERs, GRs and TRs.

Binding and drug displacement study of colchicine and bovine serum albumin in presence of azithromycin using multispectroscopic techniques and molecular dynamic simulation.

The binding and displacement interaction of colchicine and azithromycin to the model transport protein bovine serum albumin (BSA) was evaluated in this study. Azithromycin, a macrolide antibiotic, has antiviral properties and hence, has been used concomitantly with hydroxychloroquine against SARS-CoV-2. Colchicine, a natural plant product is used to treat and prevent acute gout flares. Some macrolide antibiotics are reported to have fatal drug-drug interactions with colchicine. The displacement interaction between colchicine and azithromycin on binding to BSA was evaluated using spectroscopic techniques, molecular docking and molecular dynamic simulation studies. The binding constant recorded for the binary system BSA-colchicine was 7.44 × 104 whereas, the binding constant for the ternary system BSA-colchicine in presence of azithromycin was 7.38 × 104 and were similar. Azithromycin didn't bind to BSA neither did it interfere in binding of colchicine. The results from molecular docking studies also led to a similar conclusion that azithromycin didn't interfere in the binding of colchicine to BSA. These findings are important since there is possibility of serious adverse event with co-administration of colchicine and azithromycin in patients with underlying gouty arthritis and these patients need to be continuously monitored for colchicine toxicity.

Binding Properties of DNA and Antimicrobial Peptide Chensinin-1b Containing Lipophilic Alkyl Tails.

Multidrug-resistant bacteria present an important threat to human health. In this study, due to the weak antimicrobial activity of chensinin-1b against multidrug-resistant (MDR) bacteria, three lipo-chensinin-1b peptides, including OA-C1b, LA-C1b and PA-C1b, were designed and their activities against MDR bacteria were examined. Both the OA-C1b and LA-C1b peptides exhibited potent antimicrobial activity against selected multidrug-resistant bacterial strains. In addition to the direct disruption of bacterial membranes by antimicrobial peptides, it has also been proposed that DNA is a superior intracellular target for antimicrobial peptides. ctDNA was used as a model to investigate the binding properties of DNA and lipo-chensinin-1b peptides using a variety of biophysical methods. The kinetics results of both UV-Vis and CD spectroscopy suggested that the interaction between lipo-chensinin-1b peptides and ctDNA was concentration-dependent and resulted in an increase in polynucleotide helicity. Viscosity measurements, Trp fluorescence and iodide quenching experiments indicated that nonclassical groove binding and electrostatic binding interaction modes were utilized when the peptides interacted with the ctDNA. In addition, the formation of peptide-ctDNA complexes was monitored using dynamic light scattering experiments, during which the peptide exhibited the ability to neutralize the negative charges on the surface of the ctDNA. These results promote the possibility of designing peptide-based antibiotics targeted to DNA.

Spectroscopic Methodology and Molecular Docking Studies on Changes in Binding Interaction of Felodipine with Bovine Serum Albumin Induced by Cocrystallization with ß-Resorcylic Acid.

In the present study, a novel cocrystal of felodipine (FEL) and ß-resorcylic acid (ßRA) was developed. We specially focused on the change of binding pattern with bovine serum albumin (BSA) induced by cocrystallization of FEL with ßRA. The solid characterizations and density functional theory (DFT) simulation verified that FEL-ßRA cocrystal formed in equimolar ratio (1 : 1 M ratio) through C=O…H-O hydrogen bond between C=O group in FEL and O-H group in ßRA. The binding interactions between FEL-ßRA system and BSA were studied using fluorescence spectral and molecular docking methods. Two guest molecule systems, including a physical mixture of FEL and ßRA and FEL-ßRA cocrystal were performed binding to BSA in molecular docking. According to the Kb and binding energy, the supramolecular form of FEL-ßRA system was retained during binding to BSA. Molecular docking simulation suggested that FEL and its cocrystal inserted into the subdomain IIIA (site II') of BSA. The interactions between FEL and BSA including hydrogen bonding with ASN390 residue and intermolecular hydrophobic interactions with LEU429 and LEU452 residues. However, the size of supramolecular FEL-ßRA better matched that of active cavity of BSA; the cocrystal is closely bound to BSA through hydrogen bonding with ASN390 residue and intermolecular hydrophobic interactions with LEU429, VAL432, LEU452 and ILE387 residues. This change on binding affinity of FEL to BSA induced by cocrystallization with ßRA provided theoretical basis to evaluate the transportation, distribution and metabolism of cocrystal drug.

Investigating the binding properties between antimony(V) and dissolved organic matter (DOM) under different pH conditions during the soil sorption process using fluorescence and FTIR spectroscopy.

Antimony (Sb) is listed as a priority pollutant by European Union and U.S. Environmental Protection Agency. However, reports on its environmental behavior, particularly the sorption process in soil are still limited. In this paper, Sb(V) was selected as the sorbate and the black soil as the sorbent. The initial sorption rate (k2qe,cal2) was calculated to be 0.1254 mg g-1∙min-1 and the maximum sorption amount (qm) 57.33 mg g-1. Once the dissolved organic matter (DOM) was removed from the soil, the values of k2qe,cal2 and qm went down to 0.1066 mg g-1∙min-1 and 19.01 mg g-1, respectively. These results suggested that the existence of DOM significantly influenced the mass transfer rate and sorption amount of Sb(V) in soil. In order to find out the reason why DOM exerted such an influence, the binding interaction mechanism between Sb(V) and DOM was investigated under different pH values. The protein-like and humic-like substances as well as the functional groups of CO, phenol hydroxyl, C-O, C-H, C-X and sulfur/phosphorus contributed to the formation of DOM-Sb(V)-complexes under pH of 7.0, in which the humic-like substance and the functional groups containing oxygen showed higher binding affinity for Sb(V) than protein-like substance and other functional groups, respectively. The protein-like substance and some functional groups disappeared under pH of 4.0 and 10.0. Alkaline condition resulted in a bigger impact on reducing the number of functional groups than acid condition. It can be concluded that the strongest binding interaction occurred at pH of 7.0 then followed by 4.0 and 10.0. This paper might be helpful to further studying the environmental behavior of Sb(V) in soil.

Dissecting the Structure-Activity Relationship of Galectin-Ligand Interactions.

Galectins are ß-galactoside-binding proteins. As carbohydrate-binding proteins, they participate in intracellular trafficking, cell adhesion, and cell-cell signaling. Accumulating evidence indicates that they play a pivotal role in numerous physiological and pathological activities, such as the regulation on cancer progression, inflammation, immune response, and bacterial and viral infections. Galectins have drawn much attention as targets for therapeutic interventions. Several molecules have been developed as galectin inhibitors. In particular, TD139, a thiodigalactoside derivative, is currently examined in clinical trials for the treatment of idiopathic pulmonary fibrosis. Herein, we provide an in-depth review on the development of galectin inhibitors, aiming at the dissection of the structure-activity relationship to demonstrate how inhibitors interact with galectin(s). We especially integrate the structural information established by X-ray crystallography with several biophysical methods to offer, not only in-depth understanding at the molecular level, but also insights to tackle the existing challenges.