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The aberrant aggregation of human islet amyloid polypeptide (hIAPP) or Amylin into toxic oligomers and fibrils leads to pancreatic β-cell dysfunction and progressive cell death, which is a key pathological feature of Type II diabetes mellitus (T2DM). In this study, we adopted a hybrid approach combining virtual screening and molecular dynamics (MD) simulation, with experimental validation, to identify inhibitors of hIAPP aggregation. Herein, we screened 2000 phytoconstituents from natural products using molecular docking, followed by in silico ADMET predictions. Withaferin A and Withanolide A (phytoconstituents of Ashwagandha) were found to be lead molecules with suitable drug-like properties. Next, we performed MD simulation to assess the stability and interaction dynamics of hIAPP-ligand complexes, and the effect of ligands on hIAPP fibrils. Building on the computational screening, we further carried out a comprehensive experimental analysis to validate the inhibitory effects of lead molecules. The collective experimental results from the Thioflavin T (ThT) assays, FTIR experiment, combined with Confocal and Transmission Electron Microscopy (TEM), suggest that the ligands (preferably Withanolide A) have a potent inhibitory effect against hIAPP aggregation by increasing the lag phase, reducing β-sheet content, and inhibiting fibril formation of hIAPP. For in vivo validation using Drosophila model, Withanolide A was found to mitigate hIAPP oligomer-induced toxicity by reducing apoptosis, necrosis, and oxidative stress in the Drosophila gut, as confirmed by multiple cell death staining assays and reactive oxygen species (ROS) analysis. Besides, in diabetic flies, Withanolide A lowered glucose levels, demonstrating anti-diabetic activity. Thus, this work, for the first time, suggests that Withanolide A may be a potential candidate for inhibiting hIAPP aggregation and as a T2DM drug.

This work reports the confluence of static and dynamic fluorescence quenching of rhodamine B (RhB) by chemically exfoliated molybdenum disulfide (MoS 2 ) nanosheets. Both steady state and time-resolved fluorescence quenching measurements were carried out to elucidate the process of energy transfer from RhB to MoS 2 . The interactive forces investigated through evaluation of thermodynamic parameters from temperature dependent fluorescence measurements are found to be hydrophobic in nature. The negative value of Gibbs free energy (∆ G ) indicates spontaneity of the adsorption process of RhB–MoS 2 system. The binding affinity of RhB–MoS 2 system is also investigated using UV/Vis spectrophotometer.

Amino silane magnetic nanocomposite decorated on graphene oxide (GO-Fe3O4-APTES) was successfully prepared by organic transformation reaction followed by co-precipitation method. The nanocomposite was characterised by using FT-IR, XRD, FE-SEM, TEM, EDS mapping, VSM, Raman spectroscopy, BET surface area analyzer, Zeta potential and UV-visible spectrophotometer. From TEM results we observed that 8 nm sized particles successfully modified on GO surface. The surface area of GO-Fe3O4-APTES was 57.9 m2 g−1. The magnetic Saturation value of GO-Fe3O4-APTES was 30.6 emu g−1 and the S-like magnetization of all the samples shows super paramagnetic in nature. Due to magnetic nature adsorbent, it could be easily separated from aqueous solution. GO-Fe3O4-APTES material was highly selective for Chromium (VI) removal from aqueous solution. About 91% of Chromium (VI) was removed at pH 3, 160 rpm of shaking speed, 0.3 g l−1 of adsorbent dose and 10 h of contact time. The adsorption process of Chromium (VI) on GO-Fe3O4-APTES follows Pseudo-second-order kinetic and Langmuir isotherm model because of high coefficient of determination value (R2 = 0.99). The maximum adsorption capacity (qm) of GO-Fe3O4- APTES was observed at 60.53 mg g−1. The synthesized material was desorbed with 0.5 M NaOH and recycled up to five cycles. After five cycles, the removal efficiency of Chromium (VI) possesses high efficacy towards GO-Fe3O4-APTES. Mechanistically, adsorption of Chromium (VI) follows strong electrostatic attraction between adsorbate and adsorbent. GO-Fe3O4-APTES has potential adsorbent for the adsorption of Chromium (VI) in waste water treatment. Furthermore, the GO-Fe3O4-APTES were tested for antibacterial properties against gram negative (Escherichia coli) and gram positive (Bacillus subtilis) bacterial strain. The synthesized material responds positively towards antibacterial activity.

Two pyrrolo-based compounds, 1H-pyrrolo[3,2-b]pyridine-3-carboxylic acid ( L1 ) and 1H-pyrrolo[3,2-c]pyridine-4-carboxylic acid ( L2 ), were employed for the detection of bovine serum albumin (BSA) by UV-Vis and fluorescence spectroscopic methods in phosphate buffer solution (pH = 7). In the presence of L1 and L2 , the fluorescence emission of BSA at 340 nm was quenched and concomitantly a red-shifted emission band appeared at 420 nm ( L1 )/450 nm ( L2 ). The fluorescence spectral changes indicate the protein-ligand complex formation between BSA and L1/L2 . An isothermal titration calorimetry (ITC) experiment was conducted to determine the binding ability between BSA and L1/L2 . The binding constants are found to be 4.45 ± 0.22 × 10 4 M −1 for L1 and 2.29 ± 0.11 × 10 4 M −1 for L2 , respectively. The thermodynamic parameters were calculated from ITC measurements (i.e. ∆rH = −40 ± 2 kcal/mol, ∆rG = −4.57 ± 0.22 kcal/mol and −T∆rS = 35.4 ± 1.77 kcal/mol), which indicated that the protein-ligand complex formation between L1/L2 with BSA is mainly due to the electrostatic interactions. The protein-ligand interactions were studied by performing molecular docking. Further, the antibacterial assay of L1 and L2 was conducted against gram-positive and gram-negative bacterial strains in an effort to address the difficulties caused by the co-occurrence of antimicrobial and multidrug-resistant bacteria. E. coli and S. aureus were significantly inhibited by L1 and L2 . The L1 exhibits 13, 12 and 15 mm, whereas L2 exhibits a 2, 3 and 5 mm zone of inhibition against S. aureus , S. pyogenes  and E. coli , respectively. In silico molecular docking of L1 and L2 was performed with bacterial DNA gyrase to establish the intermolecular interactions. Finally, the in vitro cytotoxicity activities of the ligands L1 and L2 have been carried out using drosophila. Graphical abstract

The binding interactions between bovine serum albumin (BSA) and three pyridine derivatives, i.e., 2-(5-bromopyridin-3-yl) acetic acid ( L1 ), 3-bromo-5-nitropyridine ( L2 ) and 2-chloro-4-nitropyridine ( L3 ), have been carried out using UV-Vis and fluorescence spectroscopic methods. Fluorescence intensity quenching is observed by adding L2 and L3 to the BSA solution. The quenched fluorescence emission is due to the static nature. An isothermal titration calorimetry (ITC) experiment shows the binding ability of L1 with BSA. The binding constants are found to be 7.23 ± 0.32 × 10 5 M −1 for L1 . The thermodynamic parameters were calculated from ITC measurements (i.e., ∆H = −2.78 ± 0.08 kcal/mol, ∆G = −5.65 ± 0.25 kcal/mol, and -T∆S = −2.87 ± 0.11 kcal/mol), which indicated that the protein-ligand complex formation between L1 and BSA is mainly due to the hydrogen bonds and van der Waals interactions. Cyclic voltammetry (CV) and structure activity and relationship (SAR) studies have been carried out to establish the relationship between ligands and proteins. Additionally, we conducted an antibacterial assay with gram-positive Staphylococcus aureus , Enterococcus faecalis , and negative bacterial strains Acinetobacter baumannii and Escherichia coli against L1 , L2 , and L3 , aiming to address the challenges posed by the co-existence of multidrug-resistant bacteria. Finally, drosophila is used to test the cytotoxicity of ligands L1 , L2 , and L3 ’s in vitro.

We have studied the effect of some conventional buffers, which are used frequently for biological research, on the thermal aggregation behavior of bovine serum albumin (BSA). The aggregation kinetics of BSA in buffer solutions were investigated by using UV–Vis spectroscopy. The buffers include sodium phosphate buffer, TRIS buffer and imidazole buffer at physiological pH (7.4). Dynamic light scattering and scanning electron microscopy have been employed to illustrate the size and morphology of protein aggregates. The molecular level interactions of buffer molecules with BSA was probed by various spectroscopic techniques, including UV–Vis, fluorescence, and circular dichroism. The results of this study reveal that the strong interactions of the buffers with protein’s folded/unfolded structures lead to stabilization/destabilization of BSA. We have also explored the possible binding sites of BSA for these buffers using a molecular docking technique.

AbstractConcanavalin A (ConA) is a plant lectin having industrial and biological applications. Concanavalin A changes conformation upon exposure to different stress conditions, like exposure to sodium dodecyl sulphate, guanidine hydrochloride, varying hydronium ion potential, etc. The conformational changes were studied using circular dichroism spectroscopy and the structural rigidity of ConA was explored using fluorescence spectroscopy, taking tryptophan as an intrinsic and 8-anilino-1-naphthalenesulfonic acid as an extrinsic fluorescence probes, in different stress conditions. ConA loses the quaternary structure in all the studied stress conditions, which further leads to denaturation of the protein. However, the mechanism of denaturation varied with the studied conditions, like different SDS concentrations and hydronium ion potentials, wherein the protein undergoes a conformational rearrangement from β -sheet to α -helix. Moreover, GdnHCl triggered complete denaturation of ConA into a predominantly random coil conformation. The results suggested that denaturation of ConA follows different pathways depending on the chemical properties and concentrations of the denaturants used.Graphical Abstract SynopsisGuanidine hydrochloride shows complete unfolding of Concanavalin A (Con A) above 2 M concentration, whereas GdnHCl between 1–2 M triggered the molten globule-like conformation. At basic pH, ConA adopts all- β -sheet conformation, and at acidic pH it retained demetallized monomeric jelly roll motif. Additionally, in the presence of SDS at >2 mM, ConA undergoes conformational rearrangement into a predominantly α -helix conformation, rather a leticn-like all- β -sheet conformation at lower concentrations of SDS.

Double-stranded DNA stabilized gold nanoparticles (Au NPs) are synthesized by chemical reduction method and characterized with different spectroscopic techniques such as UV-Visible absorption, Fourier transform infrared (FTIR), & circular-dichroism (CD) as well as transmission electron microscopy (TEM). These NPs show absorption maximum at 520 nm and size of most of the particles are of the order of 3.5 ± 1.0 nm. These Au NPs show crystalline nature as confirmed from electron diffraction pattern. The effect of formation of Au NPs on the macromolecule has been studied using infrared and circular dichroism spectroscopy. Formation of NPs causes conformational changes in the DNA molecules. These Au NPs are further used as resonant energy acceptor of fluorescence emission from dye molecules (Rhodamine 6G). The fluorescence intensity of Rhodamine 6G (R6G) is quenched in presence of Au NPs. The effect of DNA molecules on the fluorescence quenching and the rate of energy transfer from R6G molecules to Au NPs have been explored.

This study presents an analytical model to reduce the impact of wave-induced forces on a vertical seawall by introducing a floating elastic plate (EP) located at a specific distance from two bottom-standing porous structures (BSPs). The hydrodynamic interaction with the EP is described using thin plate theory, while the fluid flow through the porous medium is described by the model developed by Sollit and Cross. The resulting boundary value problem is addressed through linear potential theory combined with the eigenfunction expansion method (EEM), and model validation is achieved through consistency checks with recognized results from the literature. A comprehensive parametric analysis is performed to evaluate the influence of key system parameters such as the porosity and frictional coefficient of the BSPs, their height and width, the flexural rigidity of the EP, and the spacing between the EP and BSPs on vital hydrodynamic coefficients, including the wave force on the seawall, free surface elevation, wave reflection coefficient, and energy dissipation coefficient. The results indicate that higher frictional coefficients and higher BSP heights significantly enhance wave energy dissipation and reduce reflection, in accordance with the principle of energy conservation. Oscillatory trends observed with respect to wavenumbers in the reflection and dissipation coefficients highlight resonant interactions between the structures. Moreover, compared with a single BSP, the double BSP arrangement is more effective in minimizing the wave force on the seawall and free surface elevation in the region between the EP and the wall, even when the total volume of porous material remains unchanged. The inter-structural gap is found to play a crucial role in optimizing resonance conditions and supporting the formation of a tranquility zone. Overall, the proposed configuration demonstrates significant potential for coastal protection, offering a practical and effective solution for reducing wave loads on marine infrastructure.