Person: Sánchez Montero, José
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First Name
José
Last Name
Sánchez Montero
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Química en Ciencias Farmacéuticas
Area
Química Orgánica
Identifiers
3 results
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Item Advances in the discovery of heterocyclic-based drugs against Alzheimer’s disease(Expert Opinion on Drug Discovery, 2023) Sánchez Cebrián, Juan Domingo; Alcántara León, Andrés Rafael; González Matilla, Juan Francisco; Sánchez Montero, José; Sánchez Montero, JoséIntroduction Alzheimer’s disease is a multifactorial neurodegenerative disorder characterized by beta-amyloid accumulation and tau protein hyperphosphorylation. The disease involves interconnected mechanisms, which can be clustered into two target-packs based on the affected proteins. Pack-1 focuses on beta-amyloid accumulation, oxidative stress, and metal homeostasis dysfunction, and Pack-2 involves tau protein, calcium homeostasis, and neuroinflammation. Against this background heterocyclic system, there is a powerful source of pharmacophores to develop effective small drugs to treat multifactorial diseases like Alzheimer’s. Areas covered This review highlights the most promising heterocyclic systems as potential hit candidates with multi-target capacity for the development of new drugs targeting Alzheimer’s disease. The selection of these heterocyclic systems was based on two crucial factors: their synthetic versatility and their well-documented biological properties of therapeutic potential in neurodegenerative diseases. Expert opinion The synthesis of small drugs against Alzheimer’s disease requires a multifactorial approach that targets the key pathological proteins. In this context, the utilization of heterocyclic systems, with well-established synthetic processes and facile functionalization, becomes a crucial element in the design phases. Furthermore, the selection of hit heterocyclic should be guided by a full understanding of their biological activities. Thus, the identification of promising heterocyclic scaffolds with known biological effects increases the potential to develop effective molecules against Alzheimer’s disease.Item Analogues of cannabinoids as multitarget drugs in the treatment of Alzheimer’s disease(European Journal of Pharmacology, 2021) Fernandez, María; Villaro, Wilma; Gómez Cañas, María; García-Arencibia, Moisés; Egea, Javier; Fernández Ruiz, José Javier; Martín, María Isabel; Girón, Rocío; Sánchez Montero, José; Agis Torres, Ángel; Solano, David; Sollhuber Kretzer, Mónica; Sánchez Montero, JoséGiven that neuronal degeneration in Alzheimer's disease (AD) is caused by the combination of multiple neurotoxic insults, current directions in the research of novel therapies to treat this disease attempts to design multitarget strategies that could be more effective than the simply use of acetylcholinesterase inhibitors; currently, the most used therapy for AD. One option, explored recently, is the synthesis of new analogues of cannabinoids that could competitively inhibit the acetylcholinesterase (AChE) enzyme and showing the classic neuroprotective profile of cannabinoid compounds. In this work, molecular docking has been used to design some cannabinoid analogues with such multitarget properties, based on the similarities of donepezil and Δ9-tetrahydrocannabinol. The analogues synthesized, compounds 1 and 2, demonstrated to have two interesting characteristics in different in vitro assays: competitive inhibition of AChE and competitive antagonism at the CB1/CB2 receptors. They are highly lipophilic, highlighting that they could easily reach the CNS, and apparently presented a low toxicity. These results open the door to the synthesis of new compounds for a more effective treatment of AD.Item Developments with multi-target drugs for Alzheimer’s disease: an overview of the current discovery approaches(Expert Opinion on Drug Discovery, 2019) Sánchez Montero, José; González Matilla, Juan Francisco; Alcántara León, Andrés Rafael; Doadrio Villarejo, Antonio Luis; Sánchez Montero, JoséIntroduction: Alzheimer’s disease (AD), the most common type of dementia among older adults, is a chronic neurodegenerative pathology that causes a progressive loss of cognitive functioning with a decline of rational skills. It is well known that AD is multifactorial, so there are many different pharmacological targets that can be pursued. Areas covered: The authors highlight the strategic value of privileged scaffolds in a multi-target lead compound generation against AD, exploring the concept of multi-target design, with a special emphasis on hybrid compounds. Hence, the most promising building blocks for designing and synthesizing hybrid anti-AD drugs are shown, while also presenting the more advanced hybrid compounds. Expert opinion: The available therapeutic arsenal for AD, designed under the traditional paradigm of ‘one-drug/one target/one-disease’, is based on the inhibition of brain acetylcholinesterase (AChE) to increase acetylcholine (ACh) levels. However, this classical approach has not been sufficiently effective when used to treat any multifactor-depending pathology (cancer, diabetes or AD). The multi-target drug concept has been quickly adopted by medicinal chemists. The basic research developments reported in recent years are a solid foundation that will pave the way for the construction of future AD therapeutics.