Intelligent Pharmacy最新文献

Influenza virus transmission is largely mediated by its mutation and genome reassortment from distinct strains resulting in drug-resistances and pandemics. This necessitates the need for the discovery of more potential influenza inhibitors to prevent future epidemics. An in-silico approach was utilized here to design six new (21a-f) potential inhibitors of influenza neuraminidase (NA) using a hit compound 21 with good binding affinity, predicted activity, and pharmacokinetic properties in our previous work. The modeled activities (pEC₅₀) of the newly designed compounds (ranging between 8.188 and 7.600) were better than that of the hit compound 21 with predicted activity (pEC₅₀) of 6.0101 and zanamivir (pEC₅₀ of 5.6755) as the standard reference control used. The MolDock scores (ranging between −189.67 and −142.47 ​kcal/mol) of these newly designed compounds in the NA binding cavity were also better than the hit template 21 with a MolDock score of −125.33 ​kcal/mol and zanamivir standard drug (−136.36 ​kcal/mol). In addition, the conformational stability of the best-designed compound 21a in the NA binding cavity was further studied through the MD simulation of 100 ​ns. Moreover, the drug-likeness and ADMET predictions of these designed compounds showed their good oral bioavailability and pharmacokinetic profiling respectively. More so, the DFT calculations also revealed the relevance of these designed compounds in view of their smaller band energy gaps from the frontier molecular orbital calculations. This study could serve as a reliable in-silico perspective for the search and discovery of potential anti-influenza agents.

MAOs are flavoenzymes that aid in the oxidative deamination of neurotransmitters such as dopamine, serotonin, and epinephrine. MAO inhibitors are antidepressants that act by inhibiting neurotransmitter breakdown in the brain and controlling mood. MAO inhibitors with the chlorophenyl-chromone-carboxamide structure have been shown in investigations to be extremely effective. The current study employs in-silico screening, MD simulation, and drug kinetics evaluation, all of which are evaluated using different criteria. The study comprised 37 ligands, and three stood out as the best, with greater binding scores above the threshold value. Docking analysis found that compound 34 had the highest docking score in the series (−13.60 ​kcal/mol) and interacted with the important amino acids TYR 435, CYS 397, CYS 172, PHE 343, TYR 398, and LYS 296 required for MAO inhibitory activity. The ADMET study revealed that the compounds had drug-like properties. The results of this study could be used to develop chromone drugs that target the MAO inhibitor. The top three ligands with the highest force and work were then simulated using molecular dynamics. The protein-ligand complexes had steady trajectories throughout the 100 ns simulation, according to the data. Furthermore, the drug likeliness predicted by ADMET analysis findings indicated that the top three lead compounds had strong inhibitory efficiency, superior pharmacokinetics, and were non-toxic under physiological settings. As a result, these compounds have the potential to be exploited as possible treatment medications for PD.

A variety of medicinal compounds, including 4,6-di(1H-indol-3-yl)-1,6-dihydropyrimidin-2-amine, were synthesized through a single-step, multicomponent, stepwise reaction. In this reaction, a mixture of 1H-indole-3-Carbaldehyde, 1-(1H-indol-3-yl) ethanone and guanidine nitrate in ethanol was refluxed. The synthesized compounds were characterized using ¹H NMR and ¹³C NMR studies and their antimicrobial activities against Escherichia coli, Staphylococcus aureus, Aspergillus niger and Aspergillus flavus were evaluated. Molecular docking analysis revealed specific amino acid residues (LEU704, GLY708, LEU707, GLN711, MET749, PHE764, VAL746, MET787, MET745, LEU873, HIS874, VA; 903, MET742, ILE898, MET895, ILE899, TRP741, THR877, P HE 876, LEU701, MET780) are involved in the interaction between androgen receptor and ligand. The optimal interaction and docking score were observed (7.0 ​kcal/mol).

A number of dengue viruses can seriously impact public health, and their spread has long been a concern. The development and administration of antiviral drugs have played a crucial role in combating viral infections in recent years. These drugs have shown that they can effectively inhibit viral replication and alleviate associated viral complications. The aim of this article is to provide an overview of current evidence on the effectiveness of administered antiviral drugs in controlling viral replication and treating viral problems. In the present study, the PyRx tool was used to docked proteins and ligands. In summary, the present study shows that rosmarinic acid has remarkable docking values against various dengue viral targets. Specifically, it shows a docking value of −8.0 for DENV1-E111, -8.1 for the RNA-dependent RNA polymerase (NS5), −8.2 for the non-structural A chain protein 1 (NS1), and −8.6 for the RNA helicase. These results suggest that rosmarinic acid may have an antiviral effect against the virus's target proteins. Further research is needed to investigate the therapeutic effects of rosmarinic acid in fighting viral infections. In addition, many enzymatic activities of rosmarinic acid have been reported by the PASS (Prediction of Activity Spectra for Substances) tool. The present investigation led to the definitive conclusion that rosmarinic acid possesses remarkable antiviral properties. The present study is promising for future applications, particularly in the search for a drug molecule that can effectively combat a variety of viral infections.

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Dengue is acute tropical infectious illness, which is spread by mosquitoes, has presented a significant threat to public health worldwide. Unfortunately, there are no drugs that have been clinically proven to be effective at treating or preventing dengue. The development of some drugs is significantly hampered by our incomplete understanding of dengue pathogenesis. This short review provides a brief description of potential action against DENV of dithymoquinone to develop an anti-DENV inhibitor. In-vitro, in-vivo and clinical trials are required to establish the effectiveness and safety of dithymoquinone as an anti-dengue therapy, even though computational studies have demonstrated antiviral activity against DENV.