Person:
Sánchez Montero, José

First Name

José

Last Name

Sánchez Montero

URI

https://hdl.handle.net/20.500.14352/77626

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Farmacia

Department

Química en Ciencias Farmacéuticas

Area

Química Orgánica

Identifiers

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Now showing 1 - 10 of 11

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, José
Given 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.
Biocatalysis for the asymmetric synthesis of Active Pharmaceutical Ingredients (APIs): this time is for real
(Expert Opinion on Drug Discovery, 2022) Gonzalo, Gonzalo de; Alcántara León, Andrés Rafael; Domínguez de María, Pablo; Sánchez Montero, José; Sánchez Montero, José
Introduction Biocatalysis has emerged as a powerful and useful strategy for the synthesis of active pharmaceutical ingredients (APIs). The outstanding developments in molecular biology techniques allow nowadays the screening, large-scale production, and designing of biocatalysts, adapting them to desired reactions. Many enzymes can perform reactions both in aqueous and non-aqueous media, broadening even further the opportunities to integrate them in complex pharmaceutical multi-step syntheses. Areas covered This paper showcases several examples of biocatalysis in the pharmaceutical industry, covering examples of different enzymes, such as lipases, oxidoreductases, and transaminases, to deliver active drugs through complex synthetic routes. Examples are critically discussed in terms of reaction conditions, motivation for using an enzyme, and how biocatalysts can be integrated in multi-step syntheses. When possible, biocatalytic routes are benchmarked with chemical reactions. Expert Opinion The reported enzymatic examples are performed with high substrate loadings (>100 g L−1) and with excellent selectivity, making them inspiring strategies for present and future industrial applications. The combination of powerful molecular biology techniques with the needs of the pharmaceutical industry can be aligned, creating promising platforms for synthesis under more sustainable conditions.
On the Use of Orthoformates as an Efficient Approach to Enhance the Enzymatic Enantioselective Synthesis of (S)-Ibuprofen
(Catalysts, 2023) Khiari, Oussama; Bouzemi, Nassima; Sánchez Montero, José; Alcántara León, Andrés Rafael; Sánchez Montero, José; Alcántara León, Andrés Rafael
In this paper, we describe the effectiveness of the combination between an organic solvent system mixture with orthoformates with different chain sizes from one to four carbon atoms. These orthoesters have been used as a “water trapper/alcohol releaser molecule” to reach a notable improvement in enantioselectivity and enantiomeric excess of our target compound, (S)-2-(4-isobutylphenyl)propanoic acid (ibuprofen eutomer), during the enzymatic kinetic resolution of rac-ibuprofen using immobilized lipase B of Candida antarctica as a biocatalyst. At the same time, one of the great problems of biocatalysis in organic media has been solved by eliminating excess water in the medium that allows the reversibility of the reaction. Following the optimization of the reaction conditions, an increase in enantiomeric excess and enantioselectivity was reached by using these acyl donors in the presence of a cosolvent.
Project number: 138
Elaboración de una tabla periódica interactiva de los elementos químicos y de sus propiedades ordenadas con acceso por internet
(2017) Doadrio Villarejo, Antonio Luis; Izquierdo Barba, Isabel; Colilla Nieto, Montserrat; Martínez Alonso, África; Sánchez Salcedo, Sandra; García Fontecha, Ana; Cabañas Criado, María Victoria; Peña López, Juan; Román Zaragoza, Jesús; Salinas Sánchez, Antonio J.; Doadrio Villarejo, Juan Carlos; Gutierrez Rios, Maria Teresa; Arcos Navarrete, Daniel; Moreno Pérez, José Manuel; Vallet Regí, María Dulce Nombre; Sánchez Montero, José
Se ha construido una base de datos con las propiedades de los elementos químicos, isótopos naturales y artificiales de los elementos y el tiempo de semivida de los radiactivos, así como, la serie de la tabla periódica a la que pertenecen, carácter metálico/no metálico/metaloide, configuración electrónica y número atómico, etimología, descubridor y año de descubrimiento de cada elemento químico y de alguna/s de sus características o curiosidades más significativas.
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, José
Introduction 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.
Easy and Versatile Technique for the Preparation of Stable and Active Lipase-Based CLEA-Like Copolymers by Using Two Homofunctional Cross-Linking Agents: Application to the Preparation of Enantiopure Ibuprofen
(International Journal of Molecular Sciences, 2023) Khiari, Oussama; Bouzemi, Nassima; Sánchez Montero, José; Alcántara León, Andrés Rafael; Sánchez Montero, José; Alcántara León, Andrés Rafael
An easy and versatile method was designed and applied successfully to obtain access to lipase-based cross-linked-enzyme aggregate-like copolymers (CLEA-LCs) using one-pot, consecutive cross-linking steps using two types of homobifunctional cross-linkers (glutaraldehyde and putrescine), mediated with amine activation through pH alteration (pH jump) as a key step in the process. Six lipases were utilised in order to assess the effectiveness of the technique, in terms of immobilization yields, hydrolytic activities, thermal stability and application in kinetic resolution. A good retention of catalytic properties was found for all cases, together with an important thermal and storage stability improvement. Particularly, the CLEA-LCs derived from Candida rugosa lipase showed an outstanding behaviour in terms of thermostability and capability for catalysing the enantioselective hydrolysis of racemic ibuprofen ethyl ester, furnishing the eutomer (S)-ibuprofen with very high conversion and enantioselectivity.
Biotechnology: Impact on our Life
(Drug Design Development and Delivery Journal, 2018) Sánchez Montero, José; Sánchez Montero, José
Este trabajo aborda el uso prevalente del término "Biotecnología", evidente en los 6,480,000 resultados en Google, reflejando su integración en discusiones en diversas plataformas. El creciente interés en la biotecnología en ámbitos académicos y empresariales ha llevado a diversas definiciones, unidas por la utilización de seres vivos, procesos o productos con fines comerciales. La OCDE define la biotecnología como la aplicación de ciencia y tecnología a organismos vivos para alterar materiales con fines de producción de conocimiento, bienes y servicios. La biotecnología abarca diversos sectores como agricultura, alimentos, medio ambiente, producción industrial y energía, mostrando su naturaleza multidisciplinaria. El documento enfatiza el auge de la biotecnología blanca en la industria farmacéutica, utilizando sistemas biológicos para producir productos farmacéuticos. La biocatálisis, ejemplificada por el uso de enzimas, surge como alternativa a los procesos químicos convencionales, ofreciendo beneficios económicos y ambientales. La discusión se extiende a la controversia en torno a los alimentos transgénicos, explorando argumentos a favor y en contra de su uso. El documento también profundiza en los avances y desafíos en genómica, medicina personalizada y terapias génicas, ilustrando el impacto de la biotecnología en diversos aspectos de la vida humana y el medio ambiente. En general, el término "Biotecnología" se ha vuelto fundamental para abordar desafíos globales como el hambre, las enfermedades y la mejora general de la calidad de vida.
Docking studies for melatonin receptors
(Expert Opinion on Drug Discovery, 2018) Awad Alkozia, Hanan; Sánchez Montero, José; Doadrio Villarejo, Antonio Luis; Pintor Just, Jesús Jerónimo; Pintor Just, Jesús Jerónimo
La melatonina es una neurohormona que controla muchos procesos fisiológicos relevantes más allá del control de los ritmos circadianos. Las acciones de la melatonina son llevadas a cabo por dos tipos principales de receptores de melatonina: MT1 y MT2. Estos receptores son importantes, no solo debido a las acciones biológicas de su agonista natural, sino también porque los análogos de melatonina pueden mejorar o antagonizar su efecto biológico. El siguiente artículo describe la importancia de la melatonina como una molécula biológicamente relevante. También define los receptores para esta sustancia, así como los segundos mensajeros acoplados a estos receptores. Por último, el artículo describe los residuos de aminoácidos involucrados en el proceso de acoplamiento en los receptores de melatonina MT1 y MT2. Las acciones biológicas de la melatonina y sus interpretaciones están volviéndose más relevantes y, por lo tanto, requieren el desarrollo de nuevas herramientas farmacológicas. Comprender los mecanismos de los segundos mensajeros involucrados en las acciones de la melatonina, así como las características del acoplamiento de esta molécula a los receptores de melatonina MT1 y MT2, permitirá el desarrollo de agonistas y antagonistas más selectivos que nos ayudarán a comprender mejor esta molécula y a desarrollar nuevos compuestos terapéuticos.
Biocatalysis at Extreme Temperatures: Enantioselective Synthesis of both Enantiomers of Mandelic Acid by Transesterification Catalyzed by a Thermophilic Lipase in Ionic Liquids at 120 °C
(Catalysts, 2020) Ramos-Martín, Jesús; Khiari, Oussama; Alcántara León, Andrés Rafael; Sánchez Montero, José
The use of biocatalysts in organic chemistry for catalyzing chemo-, regio- and stereoselective transformations has become an usual tool in the last years, both at lab and industrial scale. This is not only because of their exquisite precision, but also due to the inherent increase in the process sustainability. Nevertheless, most of the interesting industrial reactions involve water-insoluble substrates, so the use of (generally not green) organic solvents is generally required. Although lipases are capable of maintaining their catalytic precision working in those solvents, reactions are usually very slow and consequently not very appropriate for industrial purposes. Increasing reaction temperature would accelerate the reaction rate, but this should require the use of lipases from thermophiles, which tend to be more enantioselective at lower temperatures, as they are more rigid than those from mesophiles. Therefore, the ideal scenario would require a thermophilic lipase capable of retaining high enantioselectivity at high temperatures. In this paper, we describe the use of lipase from Geobacillus thermocatenolatus as catalyst in the ethanolysis of racemic 2-(butyryloxy)-2-phenylacetic to furnish both enantiomers of mandelic acid, an useful intermediate in the synthesis of many drugs and active products. The catalytic performance at high temperature in a conventional organic solvent (isooctane) and four imidazolium-based ionic liquids was assessed. The best results were obtained using 1-ethyl-3-methyl imidazolium tetrafluoroborate (EMIMBF4) and 1-ethyl-3-methyl imidazolium hexafluorophosphate (EMIMPF6) at temperatures as high as 120 °C, observing in both cases very fast and enantioselective kinetic resolutions, respectively leading exclusively to the (S) or to the (R)-enantiomer of mandelic acid, depending on the anion component of the ionic liquid.
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, José
Introduction: 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.