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The enhancement of cholinergic functions via acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition is considered a valuable therapeutic strategy for the treatment of Alzheimer’s disease. This study aimed to evaluate the in vitro effect of ZINC390718, previously filtered using computational approaches, on both cholinesterases and to characterize, using a molecular dynamics (MD) simulation, the possible binding mode of this compound inside the cholinesterase enzymes. The in vitro cytotoxicity effect was also investigated using a primary astrocyte-enriched glial cell culture. ZINC390718 presented in vitro dual inhibitory activity against AChE at a high micromolar range (IC50 = 543.8 µM) and against BuChE (IC50 = 241.1 µM) in a concentration-dependent manner, with greater activity against BuChE. The MD simulation revealed that ZINC390718 performed important hydrophobic and H-bond interactions with the catalytic residue sites on both targets. The residues that promoted the hydrophobic interactions and H-bonding in the AChE target were Leu67, Trp86, Phe123, Tyr124, Ser293, Phe295, and Tyr341, and on the BuChE target, they were Asp70, Tyr332, Tyr128, Ile442, Trp82, and Glu197. The cytotoxic effect of Z390718, evaluated via cell viability, showed that the molecule has low in vitro toxicity. The in vitro and in silico results indicate that ZINC390718 can be used as chemotype for the optimization and identification of new dual cholinesterase inhibitors.

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The dual inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) is considered as an important strategy for the treatment of Alzheimer's disease. In this study, we applied the bioguided fractionations of Ocotea daphinifolia ethyl acetate active extract to furnish a fraction with high inhibitory activity for AChE and BuChE (82% and 92%, respectively). High‐performance liquid chromatography semipreparative purification of this fraction provided two new natural products: 1‐β‐D‐galactopyranosyl‐glycerol‐2,3‐heptanedionate, (1) whose complete chemical structural elucidation was made with spectrometric analysis (MS, 1D, and 2D NMR) and its minor derivative 1‐β‐D‐gulopyranosyl‐glycerol‐2,3‐heptanedionate; (2) which could be characterized by 2D 1H‐13C heteronuclear single‐quantum correlation spectra analysis. Investigation of the intermolecular interactions with cholinesterases was carried out by molecular docking studies, and results suggested that both compounds are capable to interact with the catalytic site of both enzymes. Compounds 1 and 2 interact with residues of catalytic domains and the peripheral anionic binding site of AChE and BuChE. The results are comparable to those achieved with rivastigmine and galantamine. Thus, this study provides evidence for consideration of the glycosylglycerol from O. daphnifolia as new valuable dual cholinesterases inhibitor.

In Brazil, the legislation created to regulate the use of substances and drugs subjected to special control is from Ordinance Number 344 of May 12, 1998, which establishes a standard model for prescriptions in which such substances are prescribed. This ordinance also proposes to eliminate ambiguous, illegible or incomplete prescriptions, as well as the lack of standardization of the nomenclature of prescription drugs, the correct use of the notification model, the use of abbreviations and the presence of erasures, which composes elements that may cooperate to the occurrence of mistakes. To rate prescriptions that are dispensed in a Psychosocial Care Center inside of Bahia. Cross-sectional study, based on the collection of prescriptions and psychotropic drugs notifications, kept at the pharmacy of the Psychosocial Care Center of a city of Bahia, from May 2018 to May 2019. According to the prescriptions analyzed, it was observed mistakes such as illegibility, absence of quantity of medication to be dispensed, absence of the date of issue and prescription out of date, as well as common mistakes by the prescriptive professional such as do not present their specialty. From these data was realized the necessity for more rigorous supervision and attention to the existing data in prescriptions, in order to avoid future problems, which would be minimized if it had the presence or attendance of an effective pharmacist in the service.