Cannabis sativa withdrawal syndrome is characterized mainly by psychological symptoms. By using computational tools, the aim of this study was to propose drug candidates for treating withdrawal syndrome based on the natural ligands of the cannabinoid type 1 receptor (CB1). One compound in particular, 2‐n‐butyl‐5‐n‐pentylbenzene‐1,3‐diol (ZINC1730183, also known as stemphol), showed positive predictions as a human CB1 ligand and for facile synthetic accessibility. Therefore, ZINC1730183 is a favorable candidate scaffold for further research into pharmacotherapeutic alternatives to treat C. sativa withdrawal syndrome.

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: The GSK-3β enzyme is related to neuronal cell degeneration presented in Alzheimer’s Disease (AD). The objective of this research was to propose analogues of GSK-3β inhibitors through the search for inhibitors of this enzyme, derivation of the pharmacophore patterns of those inhibitors, molecular docking, ADME/Tox prediction, molecular modifi- cations and prediction of synthetic viability. Six analogues were obtained from the inhibitor CID 57399952, since it presents favorable ADME properties and, as disadvantage, only presents mutagenicity. After modifications, all analogues presented absence of alerts of mutagenic and carcinogenic activity, both for rats and mouse, likewise all presented low risks alerts for inhibition of hERG and medium prediction of synthetic viability. It is concluded that the analogues to GSK-3β inhibitors were optimized in relation to the toxicity of template, being presented as promising drug candidates for Alzheimer’s disease treatment.

Background: Parkinson's disease (PD) is a neurodegenerative pathology common in the elderly, and it may be related to several factors, such as excessive and continuous use of drugs, alcoholism, cerebral ischemia, among others. Emphasizing that there is still no cure for PD, current pharmacological treatment aims to restore reduced dopaminergic activity in the central nervous system and manage symptoms. However, due to the different side effects caused by antiparkinsonian drugs, their use is recommended just when symptoms are considerably impairing professional performance or the patient's daily tasks. Therefore, studies for the development of new drugs have been conducted, and natural products are gaining importance due to the possibility of discovering new bioactive molecular. In this sense, this research aimed to perform the in silico study of molecules of natural origin for the treatment of PD. Methods: A search for molecules from medicinal plants was carried out, they underwent a pharmacokinetic and toxicological prediction with subsequent molecular docking study, being coupled with the MAO-B enzyme and the dopamine receptor 2. Results: The ginsenosides compounds present an unfavorable pharmacokinetic pattern, which can be explained by their molecular mass, while the other molecules present average patterns, with the exception of kavains, which obtained very satisfactory results. When it comes to toxicity, the molecules curcumin, dihydrokavain, vitexin, kavain and tetrahydrocurcumin did not exhibit any toxic alert. As for the molecular docking study, the compound curcumin stood out with a considerable number of interactions at many amino acid residues relevant to antiparkinsonian activity, both in the MAO-B enzyme and in the D2 receptor. Conclusion: Of 25 molecules of natural products, 3 are good candidates for studies of oral drugs, owing to their excellent pharmacokinetic profile and low probability of being toxic. The curcumin molecule has a great notoriety, as it obtained relevant interactions with the two proteins studied in molecular docking, speciallyin the MAO-B enzyme.