No abstract

Orange solid tetrabutylammonium fluorochromate, (C4H9)4NCrO3F, TBAFC, is easily synthesized by the reaction of tetrabutylammonium fluoride with CrO3 in a 1:1 mole ratio. Tetrabutylammonium fluorochromate(VI) is a versatile reagent for the effective and selective oxidation of organic substrates, in particular of alcohols, under mild conditions. The facile oxidation of triphenylphosphine to triphenylphosphine oxide by TBAFC in CH3CN provides clear evidence for an oxygen-transfer reaction. .

The infamous chronic neurodegenerative disease, Alzheimer's, that starts with short-term memory loss and eventually leads to gradual bodily function decline which has been attributed to the deficiency in brain neurotransmitters, acetylcholine, and butylcholine. As a matter of fact, design of compounds that can inhibit cholinesterases activities (acetylcholinesterase and butylcholinesterase) has been introduced as an efficient method to treat Alzheimer's. Among proposed compounds, bis(7)tacrine (B7T) is recognized as a noteworthy suppressor for Alzheimer's disease. Recently a new analog of B7T, cystamine-tacrine dimer is offered as an agent to detain Alzheimer's complications, even better than the parent compound. In this study, classical molecular dynamic simulations have been employed to take a closer look into the modes of interactions between the mentioned ligands and both cholinesterase enzymes. According to our obtained results, the structural differences in the target enzymes active sites result in different modes of interactions and inhibition potencies of the ligands against both enzymes. The obtained information can help to investigate those favorable fragments in the studied ligands skeletons that have raised the potency of the analog in comparison with the parent compound to design more potent multi target ligands to heal Alzheimer's disease.

Due to the multiple pathogens of Alzheimer's disease, multitarget-directed ligand (MTDL) design has been highly regarded in recent years. MTDLs are used to control several pathogens at the same time. The main objective of this research is to provide an appropriate MTDL for the treatment of Alzheimer's disease. Due to the high importance of cholinesterase inhibition, chelating metal ions and collecting free radicals in the treatment of Alzheimer's disease, we used bis(7)tacrine as an efficient inhibitor of cholinesterase and S-allylcysteine as an excellent free radical scavenger and metal chelator. Accordingly, the heptamethylene linker of bis(7)tacrine was replaced with the structure of S-allylcysteine, leading to bis (7) tacrine-SAC. Performances of the designed ligand as a new potential multitarget-directed ligand (MTDL) have been theoretically studied. Antioxidant and chelating properties of bis(7)tacrine-SAC have been investigated using density functional theory (DFT). On the other hand, the ability of the proposed ligand to inhibit cholinesterase enzymes (AChE and BChE) has been examined by employing molecular dynamics simulations. The free energies for both enzymes in complexes with the designed ligand were also extracted. In this study we demonstrated that combination of bis(7)tacrine with S-allylcysteine presents a promising multitarget-directed ligand for the treatment of Alzheimer's disease. This ligand can not only inhibit the cholinesterase enzymes very well but also acts as an efficient antioxidant and metal scavenger. The results of quantum mechanics calculations, molecular docking, MD simulation and binding free energy calculations corroborate that bis(7)tacrine-SAC can simultaneously target some of the most important pathogens of Alzheimer's disease. In general, the obtained results show this ligand can be introduced as a worthwhile candidate for the treatment of Alzheimer's disease, although more accurate investigation using experimental methods is essential.