Synthesis, Characterization and Investigation of Cross-Linked Chitosan/(MnFe₂O₄) Nanocomposite Adsorption Potential to Extract U(VI) and Th(IV)

A cross-linked chitosan/(MnFe2O4) CCsMFO nanocomposite was prepared using co-precipitation methods and used as a nanomaterial to extract U(VI) and Th(IV) from an aqueous solution based on adsorption phenomena. The contact time of experiments shows a rapid extraction process within 30 min by the CCsMFO nanocomposite. The solution pH acts a critical role in determining qm value, where pH 3.0 was the best pH value to extract both ions. The pseudo-second-order equilibrium model illustrated the kinetics equilibrium modal extraction process. Adsorption isotherm of U(VI) at pH 3.0 by CCsMFO nanocomposite is an endothermic process. In contrast, the adsorption isotherm of Th(IV) at pH 3.0 by CCsMFO nanocomposite is an exothermic process. The reusability of CCsMFO nanocomposite was tested using basic eluents as suitable conditions for the chemical stability of CCsMFO nanocomposite; the reusability results show promising results for the removal of U(VI) adsorbed onto CCsMFO nanocomposite with 77.27%, after 12 h by Na2CO3 as eluent. At the same time, the reusability results show good reusability for removal of U(VI) adsorbed onto CCsMFO nanocomposite with 21.82%, after 8 h by EDTA as eluent

Garlic as an effective antifungal inhibitor: A combination of reverse docking, molecular dynamics simulation, ADMET screening, DFT, and retrosynthesis studies

Fungal infections profoundly affect human health, causing a substantial number of infections and millions of fatalities annually on a global scale. The identification of new drugs targeting this infection is a challenge that is not yet complete. Natural products, including medicinal and aromatic plants, substances that act as sources of beneficial chemical compounds for the development of efficient therapies, are among the medicines that can be used to combat this type of infection. In this study, seven bioactive molecules derived from garlic plant as potential antifungal inhibitors were investigated using computational methods. Alliin and S-allyl-cysteine, bioactive molecules generated from garlic, showed good stability at the active site of the studied receptor (PDB code: 5TZ1). They provided binding energies of −4.80 and −4.90 Kcal/mol, and inhibition constant (Ki) values of 303.78 and 253.68 µM, respectively. Similarly, alliin and S-allyl-cysteine were stabilized in the active site of the target receptor by conventional hydrogen bonds with residues Ser507 (2.47 Å), Ser378 (3.01 Å), Met508 (2.62 Å, 3.46 Å), and His377 (3.00 Å), Ser378 (3.09 Å), Met508 (2.01 Å), Ser507 (2.26 Å), respectively. These results were confirmed by molecular dynamic simulation. The selected molecules comply with the most important drug rules such as Lipinski, Veber and Egan, have good ADME properties and are not toxic; therefore, these bioactive molecules have good pharmacokinetic properties and bioavailability. The retrosynthesis method has created a pathway for the synthesis of these candidate inhibitors. As a result, the outcomes of this study strongly suggest that Alliin, S-allyl-cysteine, are potential antifungal inhibitors in the future

Computational integration for antifungal 1,2,4-triazole inhibitors design: QSAR, molecular docking, molecular dynamics simulations, ADME/Tox, and retrosynthesis studies

Fungal infections are a growing public health problem worldwide. Despite the availability of several medicines, their efficacy is still constrained by fungal resistance. This research conducted the 2D/3D-QSAR analysis on twenty-nine triazole molecules previously evaluated for their antifungal activity. The HQSAR/B-H, CoMFA and CoMSIA models were built using twenty-three molecules in the training set. They show high Q2 values (0.646, 0.564 and 0.561, respectively) and important R2 values (0.764, 0.805 and 0.787, respectively). The predictive capacity of the established models was validated by external validation; they performed well. The contour maps derived from the HQSAR/B-H, CoMFA and CoMSIA models provide more detail to identify favorable and unfavorable groupings impacting the activity. Then, 4 proposed new triazole molecules with significant antifungal activity were suggested. In addition, the molecular docking results showed good binding energies and interactions of the proposed inhibitors in the active site of the receptor studied. The molecular dynamics and MM/PBSA methods confirmed and validated the molecular docking results. The new triazole molecules were evaluated for their oral bioavailability and toxicity using ADME/Tox properties. Finally, the retrosynthesis method created a synthetic pathway for the candidate inhibitor Z1

High-throughput virtual screening approach of natural compounds as target inhibitors of plasmepsin-II

Plasmepsin II is a key enzyme in the life cycle of the Plasmodium falciparum parasite responsible for malaria, a disease that is causing deaths on a worldwide scale. Recently, plasmepsin II enzyme has gained much importance as an attractive drug target for the investigation of antimalarial drugs. In this sense, structure-based virtual screening have been utilized as tools in the process of discovering novel natural compounds based on quinoline as potential plasmepsin II inhibitors. Among the 58 quinoline derivatives isolated from different plants was screened by utilizing docking molecular, ADMET approaches, molecular dynamics simulation and MM-PBSA binding free energy. The first step in this work is building the 3 D structures of the plasmepsin II enzyme by using the SWISS-MODEL software. The optimized structures were subjected to virtual screening by Autodock Vina, an entity implicated in PyRx software. 21 were selected based on their binding affinity. The binding modes and interactions of the top-21 selected compounds were evaluated using AutoDock 4.2. Then, the pharmacokinetic proprieties and toxicity of these compounds were evaluated using ADMET analysis. Ten compounds were predicted to have ADMET characteristics with no side effects. Compounds M49 and M53 were found to be potential inhibitors. The stability of the selected two compounds was confirmed by MD simulation and MM/PBSA calculation during 200 ns. This study can be used to predict and to design new antimalarial drugs. Communicated by Ramaswamy H. Sarma</p

Design of new α-glucosidase inhibitors through a combination of 3D-QSAR, ADMET screening, molecular docking, molecular dynamics simulations and quantum studies

Diabetes mellitus is a chronic and non-infectious metabolic disorder caused by insufficient insulin secretion. This study investigated a set of thirty-one 4-amino-1,2,4-triazole derivatives, experimentally evaluated for their α-glucosidase activity against diabetes mellitus, using the three-dimensional quantitative structure–activity relationship (3D-QSAR) approach. The recommended CoMFA and CoMSIA/EHA models showed good predictive ability, manifested by high R2 values and important Q2 values. The molecular structural features offered by the CoMFA and CoMSIA/EHA contour maps had a significant impact on the determination of appropriate groups to enhance activity. Hence, four new 4-amino-1,2,4-triazole inhibitors were proposed and designed with good predicted α-glucosidase activity. The pharmacological and ADME-Tox properties of the four recommended molecules were predicted and examined. Molecular docking studied the interaction modes between the targeted receptor and 4-amino-1,2,4-triazole derivatives; it showed good stability for the new title molecule M1. Furthermore, molecular dynamics simulation at 100 ns and MM/PBSA approach results demonstrated an acceptable stability and the interactive force of the compound M1. Finally, the most nucleophilic and electrophilic centers of the compounds C25 and M1 were determined using quantum analysis. The current work encourages further experimental and scientific research on M1 molecule as a potent α-glucosidase inhibitor