Discovering phenoxy acetohydrazide derivatives as urease inhibitors and molecular docking studies.

Helicobacter pylori causes severe stomach disorders and the use of enzyme inhibitors for treatment is one of the possible therapies. The great biological potential of imine analogs as urease inhibitors has been the focus of researchers in past years. In this regard, we have synthesized twenty-one derivatives of dichlorophenyl hydrazide. These compounds were characterized by different spectroscopic techniques i.e. NMR and HREI-MS. Compounds 2 and 10 were found to be the most active in the series. Structure-activity relationship has been established for all compounds based on different substituents attached to the phenyl ring that play a vital role in enzyme inhibition. From the structure-activity relationship, it has been observed that these analogs showed excellent potential for urease and can be an alternate therapy in the future. The molecular docking study was performed to further explore the binding interactions of synthesized analogs with enzyme active sites.Communicated by Ramaswamy H. Sarma.

Identification of Disalicyloyl Curcumin as a Potential DNA Polymerase Inhibitor for Marek's Disease Herpesvirus: A Computational Study Using Virtual Screening and Molecular Dynamics Simulations.

Marek's disease virus (MDV) is a highly contagious and persistent virus that causes T-lymphoma in chickens, posing a significant threat to the poultry industry despite the availability of vaccines. The emergence of new virulent strains has further intensified the challenge of designing effective antiviral drugs for MDV. In this study, our main objective was to identify novel antiviral phytochemicals through in silico analysis. We employed Alphafold to construct a three-dimensional (3D) structure of the MDV DNA polymerase, a crucial enzyme involved in viral replication. To ensure the accuracy of the structural model, we validated it using tools available at the SAVES server. Subsequently, a diverse dataset containing thousands of compounds, primarily derived from plant sources, was subjected to molecular docking with the MDV DNA polymerase model, utilizing AutoDock software V 4.2. Through comprehensive analysis of the docking results, we identified Disalicyloyl curcumin as a promising drug candidate that exhibited remarkable binding affinity, with a minimum energy of -12.66 Kcal/mol, specifically targeting the DNA polymerase enzyme. To further assess its potential, we performed molecular dynamics simulations, which confirmed the stability of Disalicyloyl curcumin within the MDV system. Experimental validation of its inhibitory activity in vitro can provide substantial support for its effectiveness. The outcomes of our study hold significant implications for the poultry industry, as the discovery of efficient antiviral phytochemicals against MDV could substantially mitigate the economic losses associated with this devastating disease.

Facile one-step synthesis of gold nanoparticles using Viscum album and evaluation of their antibacterial potential.

Nanostructure gold nanoparticles (Au NPs) are well-known biological active materials, synthesised under different environment-friendly approaches that has gained significant interest in the field of biomedicine. This study investigated a novel, fast, easy, cost-effective and the eco-friendly method to synthesise Au NPs from mediated Viscum album Linn plant extract, where the plant metabolites act as stabilising and reducing agents. The synthesised Au NPs were analysed by UV/Vis spectroscopy that gave strong signals and a sharp absorption peak at 545nm due to the presence of surface plasmon resonance (SPR) bands. In addition, energy dispersive X-ray spectroscopy (EDX) showed that strong signals of Au NPs appeared at 9.7 and 2.3keV, as the rays of light passed. X-ray diffraction recognised the crystalline material and provided information on the cell unit that the synthesised Au NPs are face-centreed cubic in structure. The diffraction of X-ray spectra showed intense peaks at 38.44°, 44.7°, 44.9° and 77.8°. The mediated V. album plant extracts and synthesised Au NPs were screened against gram-positive and gram-negative (Enterobacter , Salmonella typhi , Escheria coli and Bacillus subtilis ) bacterial strains, confirming their antibacterial potential. Au NPs showed strong antibacterial activity due to its unique steric configuration. Au NPs damaged bacterial cell membrane leading to the leakage of the cytoplasm and death of the cell.

Investigation on Crystal-Structure, Thermal and Electrical Properties of PVDF Nanocomposites with Cobalt Oxide and Functionalized Multi-Wall-Carbon-Nanotubes.

Nanocomposites of polyvinylidene fluoride (PVDF) with dimensional (1D) cobalt oxide (Co3O4) and f-MWCNTs were prepared successfully by the solution casting method. The impact of 1D Co3O4 filler and 1D Co3O4/f-MWCNTs co-fillers on the structural, thermal, and electrical behavior of PVDF were studied. The crystal structural properties of pure PVDF and its nanocomposite films were studied by XRD, which revealed a significant enhancement of ß-phase PVDF in the resulting nanocomposite films. The increase in ß-phase was further revealed by the FTIR spectroscopic analysis of the samples. TG, DTA, and DSC analyses confirmed an increase in thermal stability of PVDF with the addition of nano-fillers as well as their increasing wt.%. From impedance spectroscopic studies, it was found that the DC conductivity of PVDF increases insignificantly initially (up to 0.1 wt.% of nano-fillers addition), but a significant improvement in DC conductivity was found at higher concentrations of the nano-fillers. Furthermore, it was observed that the DC conductivity decreases with frequency. The increase in DC conductivity corresponded to the strong interactions of nano-fillers with PVDF polymer chains.

Synthesis and Characterization of Ni Nanoparticles via the Microemulsion Technique and Its Applications for Energy Storage Devices.

Herein, a unique synthetic approach called microemulsion is used to create nickel nanoparticles (Ni-NPs). SEM, TEM, EDX, and XRD techniques were employed for the investigation of morphology and structures of the synthesized material. Electrons from electroactive components are transferred to external circuits by Ni-NPs' superior electrical conductivity and interconnected nanostructures, which also provide a large number of channels for ion diffusion and additional active sites. The experimental findings showed that as a positive electrode for supercapacitors (SC), Ni-NPs had an outstanding ability to store charge, with a dominant capacitive charge storage of 72.4% when measured at 10 mV/s. Furthermore, at 1 A/g, Ni-NP electrodes exhibit a maximum capacitance of 730 F/g. Further, the Ni-NP electrode retains 92.4% of its capacitance even for 5000 cycles, highlighting possible applications for it in the developing field of renewable energy. The current study provides a new method for producing high-rate next-generation electrodes for supercapacitors.

Intracellular Activation of Anticancer Therapeutics Using Polymeric Bioorthogonal Nanocatalysts.

Bioorthogonal catalysis provides a promising strategy for imaging and therapeutic applications, providing controlled in situ activation of pro-dyes and prodrugs. In this work, the use of a polymeric scaffold to encapsulate transition metal catalysts (TMCs), generating bioorthogonal "polyzymes," is presented. These polyzymes enhance the stability of TMCs, protecting the catalytic centers from deactivation in biological media. The therapeutic potential of these polyzymes is demonstrated by the transformation of a nontoxic prodrug to an anticancer drug (mitoxantrone), leading to the cancer cell death in vitro.

Intracellular Activation of Bioorthogonal Nanozymes through Endosomal Proteolysis of the Protein Corona.

Bioorthogonal activation of prodrugs provides a strategy for on-demand on-site production of therapeutics. Intracellular activation provides a strategy to localize therapeutics, potentially minimizing off-target effects. To this end, nanoparticles embedded with transition metal catalysts (nanozymes) were engineered to generate either "hard" irreversible or "soft" reversible coronas in serum. The hard corona induced nanozyme aggregation, effectively inhibiting nanozyme activity, whereas only modest loss of activity was observed with the nonaggregating soft corona nanozymes. In both cases complete activity was restored by treatment with proteases. Intracellular activity mirrored this reactivation: endogenous proteases in the endosome provided intracellular activation of both nanozymes. The role of intracellular proteases in nanozyme reactivation was verified through treatment of the cells with protease inhibitors, which prevented reactivation. This study demonstrates the use of intracellular proteolysis as a strategy for localization of therapeutic generation to within cells.

New triazinoindole bearing thiazole/oxazole analogues: Synthesis, α-amylase inhibitory potential and molecular docking study.

New triazinoindole bearing thiazole/oxazole analogues (1-21) were synthesized and characterized through spectroscopic techniques such as HREI-MS, 1H and 13C NMR. The configuration of compound 2i and 2k was confirmed through NOESY. All analogues were evaluated against α-amylase inhibitory potential. Among the synthesized analogues, compound 1h, 1i, 1j, 2a and 2f having IC50 values 1.80 ±â€¯0.20, 1.90 ±â€¯0.30, 1.2 ±â€¯0.30, 1.2 ±â€¯0.01 and 1.30 ±â€¯0.20 µM respectively, showed excellent α-amylase inhibitory potential when compared with acarbose as standard (IC50 = 0.91 ±â€¯0.20 µM). All other analogues showed good to moderate inhibitory potential. Structural activity relationship (SAR) has been established and binding interactions were confirmed through docking studies.

Synthesis, anti-leishmanial and molecular docking study of bis-indole derivatives.

We have synthesized new series of bisindole analogs (1-27), characterized by 1HNMR and HR-EI-MS and evaluated for their anti-leishmanial potential. All compounds showed outstanding inhibitory potential with IC50 values ranging from 0.7 ± 0.01 to 13.30 ± 0.50 µM respectively when compared with standard pentamidine with IC50 value of 7.20 ± 0.20 µM. All analogs showed greater potential than standard except 10, 19 and 23 when compared with standard. Structure activity relationship has been also established for all compounds. Molecular docking studies were carried out to understand the binding interaction of active molecules.

Synthesis and molecular docking study of piperazine derivatives as potent inhibitor of thymidine phosphorylase.

Thymidine phosphorylase triggers the phosphorylation of pyrimidine base to thymine and 2-deoxyribose 1-phosphate which undergoes dephosphorylation to 2-deoxyribose. It plays a role in tumor angiogenesis which is referred to the development of blood vessels during tumor growth and therefore is an attractive drug target. Keeping in view the greater importance of its inhibition, here in this study we have synthesized piperazine analogs (1-18) and evaluated for thymidine phosphorylase inhibitory activity. All analogs showed potent inhibitory potential with IC50 values ranging between 0.2 ±â€¯0.01 and 42.20 ±â€¯0.70 µM when compared with standard 7-Deazaxanthine (IC50 value of 38.68 ±â€¯1.12 µM). Structure activity relationship has been also established for all newly synthesized compounds. Molecular docking studies revealed that these compounds established stronger hydrogen bonding networks with active site residues of enzyme.

Synthesis, molecular docking study and in vitro thymidine phosphorylase inhibitory potential of oxadiazole derivatives.

We have synthesized oxadiazole derivatives (1-16), characterized by 1H NMR, 13C NMR and HREI-MS and screened for thymidine phosphorylase inhibitory potential. All derivatives display varied degree of thymidine phosphorylase inhibition in the range of 1.10 ±â€¯0.05 to 49.60 ±â€¯1.30 µM when compared with the standard inhibitor 7-Deazaxanthine having an IC50 value 38.68 ±â€¯1.12 µM. Structure activity relationships (SAR) has been established for all compounds to explore the role of substitution and nature of functional group attached to the phenyl ring which applies imperious effect on thymidine phosphorylase activity. Molecular docking study was performed to understand the binding interaction of the most active derivatives with enzyme active site.

Synthesis, in vitro α-glucosidase inhibitory potential and molecular docking study of thiadiazole analogs.

α-Glucosidase is a catabolic enzyme that regulates the body's plasma glucose levels by providing energy sources to maintain healthy functioning. 2-Amino-thiadiazole (1-13) and 2-amino-thiadiazole based Schiff bases (14-22) were synthesized, characterized by 1H NMR and HREI-MS and screened for α-glucosidase inhibitory activity. All twenty-two (22) analogs exhibit varied degree of α-glucosidase inhibitory potential with IC50 values ranging between 2.30 ±â€¯0.1 to 38.30 ±â€¯0.7 µM, when compare with standard drug acarbose having IC50 value of 39.60 ±â€¯0.70 µM. Among the series eight derivatives 1, 2, 6, 7, 14, 17, 19 and 20 showed outstanding α-glucosidase inhibitory potential with IC50 values of 3.30 ±â€¯0.1, 5.80 ±â€¯0.2, 2.30 ±â€¯0.1, 2.70 ±â€¯0.1, 2.30 ±â€¯0.1, 5.50 ±â€¯0.1, 4.70 ±â€¯0.2, and 5.50 ±â€¯0.2 µM respectively, which is many fold better than the standard drug acarbose. The remaining analogs showed good to excellent α-glucosidase inhibition. Structure activity relationship has been established for all compounds. The binding interactions of these compounds were confirmed through molecular docking.

Modulating the Catalytic Activity of Enzyme-like Nanoparticles Through their Surface Functionalization.

The inclusion of transition metal catalysts into nanoparticle scaffolds permits the creation of catalytic nanosystems (nanozymes) able to imitate the behaviour of natural enzymes. Here we report the fabrication of a family of nanozymes comprised of bioorthogonal ruthenium catalysts inserted in the protective monolayer of gold nanoparticles. By introducing simple modifications to the functional groups at the surface of the nanozymes, we have demonstrated control over the kinetic mechanism of our system. Cationic nanozymes with hydrophobic surface functionalities tend to replicate the classical Michaelis Menten model, while those with polar groups display substrate inhibition behaviour, a key mechanism present in 20 % of natural enzymes. The structural parameters described herein can be used for creating artificial nanosystems that mimic the complexity observed in cell machinery.

Synthesis of 4-thiazolidinone analogs as potent in vitro anti-urease agents.

4-Thiazolidinone analogs 1-20 were synthesized, characterized by (1)H NMR and EI-MS and investigated for urease inhibitory activity. All twenty (20) analogs exhibited varied degree of urease inhibitory potential with IC50 values 1.73-69.65µM, if compared with standard thiourea having IC50 value of 21.25±0.15µM. Among the series, eight derivatives 3, 6, 8, 10, 15, 17, 19, and 20 showed outstanding urease inhibitory potential with IC50 values of 9.34±0.02, 14.62±0.03, 8.43±0.01, 7.3±0.04, 2.31±0.002, 5.75±0.003, 8.81±0.005, and 1.73±0.001µM, respectively, which is better than the standard thiourea. The remaining analogs showed good to excellent urease inhibition. The binding interactions of these compounds were confirmed through molecular docking studies.

Triazinoindole analogs as potent inhibitors of α-glucosidase: synthesis, biological evaluation and molecular docking studies.

A new series of triazinoindole analogs 1-11 were synthesized, characterized by EI-MS and (1)H NMR, evaluated for α-glucosidase inhibitory potential. All eleven (11) analogs showed different range of α-glucosidase inhibitory potential with IC50 value ranging between 2.46±0.008 and 312.79±0.06 µM when compared with the standard acarbose (IC50, 38.25±0.12 µM). Among the series, compounds 1, 3, 4, 5, 7, 8, and 11 showed excellent inhibitory potential with IC50 values 2.46±0.008, 37.78±0.05, 28.91±0.0, 38.12±0.04, 37.43±0.03, 36.89±0.06 and 37.11±0.05 µM respectively. All other compounds also showed good enzyme inhibition. The binding modes of these analogs were confirmed through molecular docking.