Background: Alzheimer's disease is a progressive neurodegenerative process of multifactorial characteristics. This disease follows the natural aging process, affecting mainly people over 65 years. Pharmacotherapeutic treatment currently combats symptoms related to cognitive function. Several targets begin to attract the interest of the scientific community to develop new drug candidates, which have better pharmacokinetic and lower toxicity parameters. Objective: The present study aims to design new candidates for acetylcholinesterase/β-secretase (AChE/BACE1) multitarget inhibitor drugs. Method: 17 natural products were selected from the literature with anticholinesterase activity and 1 synthetic molecule with inhibitory activity for BACE1. Subsequently, the molecular docking study was performed, followed by the derivation of the pharmacophoric pattern and prediction of pharmacokinetic and toxicological properties. Finally, the hybrid prototype was designed. Results: All selected molecules showed interactions with their respective target enzymes. Derivation of the pharmacophoric pattern from molecules that interacted with the AChE enzyme resulted in 3 pharmacophoric regions: an aromatic ring, an electron-acceptor region and a hydrophobic region. The molecules showed good pharmacokinetic and toxicological results, showing no warnings of mutagenicity and/or carcinogenicity. After the hybridization process, three hybrid molecules were obtained, which showed inhibitory activity for both targets. Conclusion: It is concluded that research in the field of medicinal chemistry is advancing towards the discovery of new drug candidates that bring a better quality of life to patients with AD.

Alzheimer Farmacoterapia Acetilcolinesterase BACE1 GSK3β. A Doença de Alzheimer (DA) provém de um processo neurodegenerativo progressivo de característica multifatorial que acompanha o processo de envelhecimento natural do ser humano. O tratamento farmacoterapêutico, atualmente empregado, consiste, basicamente, em controlar os sintomas, principalmente os relacionados com a função cognitiva, isto é, memória e aprendizado. Devido a sua característica multifatorial, vários alvos começam a despertar o interesse da comunidade científica, no intuito de desenvolver novos candidatos a fármacos, que apresentem melhores parâmetros farmacocinéticos e menor toxicidade. Este artigo tem como objetivo demonstrar, através de uma revisão bibliográfica, diferentes alvos para o tratamento farmacoterapêutico, tais como: acetilcolinesterase (AChE), beta secretase (BACE1) e a glicogênio sintase quinase 3β; bem como moléculas que já apresentam comprovada capacidade de interação e inibição com estes alvos, inclusive, as que já estão em fases de testes clínicos. Conclui-se que as pesquisas estão avançando, cada vez mais, em direção ao descobrimento de novos candidatos a fármacos com maior seletividade e que possam trazer uma melhor qualidade de vida aos pacientes portadores de DA.

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Every day, the questions about Cannabis sativa ability to cause chemical dependence are closed with the considerable increase in the demand for treatment of addicts to this plant. Most drug addicts submitted to treatment have difficulty in achieving and maintaining abstinence from Cannabis due to the appearance of symptoms as irritability, anxiety, desire to consume marijuana, decreased quality and quantity of sleep, and change in appetite, weight loss, and physical discomfort, besides emotional and behavioral symptoms. The neurobiological basis for the withdrawal syndrome, that is, withdrawal of Cannabis, was established after the discovery of the endogenous cannabinoid system, identification of CB1 and CB2 cannabinoid receptors, and demonstrations of precipitated removal with antagonists of these receptors. The chapter discusses the main studies currently conducted for the treatment of withdrawal syndrome based on bioligands that act directly on the CB1 cannabinoid receptor.