Quantum processing of cytidine derivatives and evaluating their in silico interactions with the COVID-19 main protease

This work was performed by the importance of exploring possible medications for COVID-19 pandemic. In this regard, cytidine (Cyd) derivatives were investigated to reach a point to see their benefit of employing for the purpose. Each of halogenated models of Cyd including CydF, CydCl, CydBr, and CydI were investigated in addition to the original CydH model. Density functional theory (DFT) based quantum processing were performed to obtain stabilized structures in addition to evaluation of frontier molecular orbitals features. Next, molecular docking (MD) simulations were performed to reach a point of formations of interacting ligand-target complexes. Among the investigated models CydH and CydI were working better than other model for reaching the purpose of this work, in which the derived CydI model was indeed the ligand with the highest suitability for formation of ligand-target complexes. As a consequence, such ligands of original and halogenated Cyd models might work for inhibition of main protease (MPro) enzyme of COVID-19 based on the obtained meaningful vales for complex strengths in addition interacting with the amino acids of active site. More precisely, the CydI model could be proposed as promising ligand for showing the inhibitory effects towards the MPro target of COVID-19.

A DNA Aptameric Ligand of Human Transferrin Receptor Generated by Cell-SELEX

General cancer-targeted ligands that can deliver drugs to cells have been given considerable attention. In this paper, a high-affinity DNA aptamer (HG1) generally binding to human tumor cells was evolved by cell-SELEX, and was further optimized to have 35 deoxynucleotides (HG1-9). Aptamer HG1-9 could be taken up by live cells, and its target protein on a cell was identified to be human transferrin receptor (TfR). As a man-made ligand of TfR, aptamer HG1-9 was demonstrated to bind at the same site of human TfR as transferrin with comparable binding affinity, and was proved to cross the epithelium barrier through transferrin receptor-mediated transcytosis. These results suggest that aptamer HG1-9 holds potential as a promising ligand to develop general cancer-targeted diagnostics and therapeutics.

Comparison of 3-carbethoxy-4-phenyl-but-3-en-2-one and methylene quinuclidinone as a ligand to reactivate mutant p53: molecular docking study in three types of crystal structure mutant p53: 2BIM, 2JIY, and 2J21

The existence of a large number of mutant p53 in cancer cell nuclei gives a poor prognosis. However, mutant p53 existence creates a challenge to design a new anticancer compound targeted to mutant p53. The 3-carbethoxy-4-phenyl-but-3-en-2-one is a novel compound that was designed as an anticancer agent targeted to mutant p53. Further evaluation of this compound was done by in silico examination employing Auto Dock Vina as molecular docking software. Molecular docking results denoted that 3-carbethoxy-4-phenyl-but-3-en-2-one had lower binding energy than methylene quinuclidinone (MQ). Visual inspection of the docking results denoted that 3-carbethoxy-4-phenyl-but-3-en-2-one docked in the binding pocket crystal structures of mutant p53 (2BIM, 2J1Y, and 2J21), forming a hydrogen bonding or hydrophobic interaction with Cys-124, and the distance between double bonds of α, β-unsaturated of 3-carbethoxy-4-phenyl-but-3-en-2-one with –SH group of Cys-124 were shorter than MQ. These results demonstrated that 3-carbethoxy-4-phenyl-but-3-en-2-one is a promising ligand to mutant p53 in many types of mutations and predicted to have better activity than MQ as a mutant p53 reactivator especially in cancers with mutation type Arg-273-His and Arg-245-Trp.

A comparative evaluation of calix[4]arene-1,3-crown-6 as a ligand for selected divalent cations of radiopharmaceutical interest

The stability constants of the promising ligand calix[4]arene-1,3-crown-6 and divalent metals of radiopharmaceutical interest: lead, barium, and strontium, were determined via NMR and UV/Vis techniques.

A practical method for the generation of organoarsenic nucleophiles towards the construction of a versatile arsenic library

Organoarsenic nucleophiles were easily and safely prepared, leading to a practical method for As–C bond formation. Promising ligand structures such as asymmetric and bidentate types can be widely constructed by the present method.

Crystal structure and hydrogen bonded network of new cadmium hybrid complex

Cadmium complexes exhibit extensive potential applications in many fields, such as magnetism materials, biological active materials, optical device and catalysis materials [1]. The reported compound [Tetrakis(5-amino-3-carboxy-1H-1,2,4-triazol-4-ium) hexachloridocadmate (II) tetrahydrate (1) ] was prepared as part of our ongoing investigations of hydrogen-bonding interactions in the crystal structures of metal-protonated N-aromatic heterocyclic hybrid frameworks [2]. 5-Amino-1H-1,2,4-triazole-3-carboxylic acid arises as a promising ligand which can be employed in the preparation of coordination compounds as a consequence of its multiple buildings sites and its basic nitrogen capable of associating with a proton H+ in acid solution [3]. The single-crystal X-ray structure analysis revealed that (1) crystallizes in the monoclinic P-1 space group, the Cd(II) atom is located at a crystallographic inversion centre. The latter ion is octahedrally coordinated by six chloride anions, Due to the presence of a considerable number of proton donors and acceptors, the crystal structure is rich in hydrogen bonding interactions which led to the formation of discrete cation layers spaced by hexachloridocadmate anions. Examination of the cation-anion interactions reveals that N–H...Cl hydrogen bonding are the major packing interactions, It appears that the layered structure results from the octahedral [CdCl6]2- anions along with its ability to form hydrogen bonds in different directions, intermolecular hydrogen bonding interactions between the chloride atom and oxygen atoms of water molecules interconnect the layers into a three-dimensional framework.

Cholinergic Depletion in Alzheimer’s Disease Shown by [18F]FEOBV Autoradiography

Rationale. Alzheimer’s Disease (AD) is a neurodegenerative condition characterized in part by deficits in cholinergic basalocortical and septohippocampal pathways. [18F]Fluoroethoxybenzovesamicol ([18F]FEOBV), a Positron Emission Tomography ligand for the vesicular acetylcholine transporter (VAChT), is a potential molecular agent to investigate brain diseases associated with presynaptic cholinergic losses. Purpose. To demonstrate this potential, we carried out an [18F]FEOBV autoradiography study to compare postmortem brain tissues from AD patients to those of age-matched controls. Methods. [18F]FEOBV autoradiography binding, defined as the ratio between regional grey and white matter, was estimated in the hippocampus (13 controls, 8 AD) and prefrontal cortex (13 controls, 11 AD). Results. [18F]FEOBV binding was decreased by 33% in prefrontal cortex, 25% in CA3, and 20% in CA1. No changes were detected in the dentate gyrus of the hippocampus, possibly because of sprouting or upregulation toward the resilient glutamatergic neurons of the dentate gyrus. Conclusion. This is the first demonstration of [18F]FEOBV focal binding changes in cholinergic projections to the cortex and hippocampus in AD. Such cholinergic synaptic (and more specifically VAChT) alterations, in line with the selective basalocortical and septohippocampal cholinergic losses documented in AD, indicate that [18F]FEOBV is indeed a promising ligand to explore cholinergic abnormalities in vivo.