A5054669743- Cholinesterase and Neurodegenerative Diseases
- Genomics, phytochemicals, and oxidative stress
- Computational Drug Discovery Methods
- Chemical synthesis and alkaloids
- Alzheimer's disease research and treatments
- Nicotinic Acetylcholine Receptors Study
- Circadian rhythm and melatonin
- Tryptophan and brain disorders
- Free Radicals and Antioxidants
- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Synthesis and biological activity
- Biochemical Acid Research Studies
- Synthesis of heterocyclic compounds
- Synthesis and Biological Evaluation
- Medicinal Plants and Neuroprotection
- vaccines and immunoinformatics approaches
- Piperaceae Chemical and Biological Studies
- Synthetic Organic Chemistry Methods
- Synthesis and Reactions of Organic Compounds
- Bioactive Compounds and Antitumor Agents
- Asymmetric Synthesis and Catalysis
- Synthesis and Reactivity of Heterocycles
Instituto de Química Médica
2020-2025
Consejo Superior de Investigaciones Científicas
2020-2025
Universitat Politècnica de Catalunya
2023-2024
Hospital Universitario Reina Sofía
2022-2024
Universidad Autónoma de Madrid
2014-2023
Universidad de Alcalá
2023
Centro de Investigación Biomédica en Red
2018-2023
Universidad Rey Juan Carlos
2023
Centro de Investigación en Red en Enfermedades Cardiovasculares
2023
Aarhus University
2023
Here we report an electrophile-triggered, secondary amine-catalyzed, enantioselective dearomatisation process that converts simple planar anisidine derivatives into complex tricyclic structures containing a quaternary stereogenic centre embedded within densely functionalised molecule.
Abstract Endothelial cell senescence is a hallmark of vascular aging that predisposes to disease. We aimed explore the capacity renin–angiotensin system (RAS) heptapeptide angiotensin (Ang)‐(1‐7) counteract human endothelial and identify intracellular pathways mediating its potential protective action. In umbilical vein (HUVEC) cultures, Ang II promoted senescence, as revealed by enhancement in senescence‐associated galactosidase (SA‐β‐gal+) positive staining, total telomeric DNA damage,...
Novel multifunctional tacrines for Alzheimer's disease were obtained by Ugi-reaction between ferulic (or lipoic acid), a melatonin-like isocyanide, formaldehyde, and tacrine derivatives, according to the antioxidant additive approach in order modulate oxidative stress as therapeutic strategy. Compound 5c has been identified promising permeable agent showing excellent properties, strong cholinesterase inhibitory activity, less hepatotoxicity than tacrine, best neuroprotective capacity, being...
Tacripyrines (1−14) have been designed by combining an AChE inhibitor (tacrine) with a calcium antagonist such as nimodipine and are targeted to develop multitarget therapeutic strategy confront AD. selective potent inhibitors in the nanomolar range. The mixed type inhibition of hAChE activity compound 11 (IC50 105 ± 15 nM) is associated 30.7 8.6% proaggregating action on Aβ moderate self-aggregation (34.9 5.4%). Molecular modeling indicates that binding PAS mainly involves (R)-11...
In this work we describe the synthesis and biological evaluation of tacrine-1,4-dihydropyridine (DHP) hybrids (3-11). These multipotent molecules are result juxtaposition an acetylcholinesterase inhibitor (AChEI) such as tacrine (1) a 1,4-DHP nimodipine (2). Compounds 3-11 very selective potent AChEIs show excellent neuroprotective profile moderate Ca2+ channel blockade effect. Consequently, these new potential drugs for treatment Alzheimer's disease.
Melatonin has been widely studied as a protective agent against oxidative stress. However, the molecular mechanisms underlying neuroprotection in neurodegeneration and ischemic stroke are not yet well understood. In this study, we evaluated neuroprotective/antioxidant mechanism of action melatonin organotypic hippocampal cultures (OHCs) photothrombotic model vivo. (0.1, 1, 10 μM) incubated postoxygen glucose deprivation (OGD) showed concentration-dependent protection; maximum protection was...
Abstract The formation of neurofibrillary tangles (NFTs), oxidative stress and neuroinflammation have emerged as key targets for the treatment Alzheimer’s disease (AD), most prevalent neurodegenerative disorder. These pathological hallmarks are closely related to over-activity enzyme GSK3β downregulation defense pathway Nrf2-EpRE observed in AD patients. Herein, we report synthesis pharmacological evaluation a new family multitarget 2,4-dihydropyrano[2,3- c ]pyrazoles dual inhibitors Nrf2...
Abstract Alterations in autophagy are increasingly being recognized the pathogenesis of proteinopathies like Alzheimer's disease ( AD ). This study was conducted to evaluate whether melatonin treatment could provide beneficial effects an Alzheimer model related tauopathy by improving autophagic flux and, thereby, prevent cognitive decline. The injection AAV ‐ hT au P301L viral vectors and treatment/injection with okadaic acid were used achieve mouse human ex vivo, vivo tau‐related models....
1,8-Naphthyridine derivatives related to 17 (ITH4012), a neuroprotective compound reported by our research group, have been synthesized. In general, they shown better inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) than most tacrine previously synthesized in laboratory. The compounds presented an interesting profile SH-SY5Y neuroblastoma cells stressed with rotenone/oligomycin A. Moreover, 14 (ethyl...
Abstract A gram‐scale catalytic enantioselective formal synthesis of morphine is described. The key steps the involve an ortho–para oxidative phenolic coupling and a highly diastereoselective “desymmetrization” resulting cyclohexadienone that generates three four morphinan ring junction stereocenters in one step. stereochemistry controlled from single carbinol center installed through hydrogenation. These transformations enabled preparation large quantities intermediates could support...
C5-unsubstituted-C6-aryl-1,4-dihydropyridines were prepared by a CAN-catalyzed multicomponent reaction from chalcones, β-dicarbonyl compounds, and ammonium acetate. These compounds able to block Ca(2+) entry after depolarizing stimulus showed an improved Cav1.3/Cav1.2 selectivity in comparison with nifedipine. Furthermore, they protect neuroblastoma cells against overload oxidative stress models. Their ratio makes them highly interesting for the treatment of neurological disorders where...
Neurodegenerative diseases are a major problem afflicting ageing populations; however, there no effective treatments to stop their progression. Oxidative stress and neuroinflammation common factors in pathogenesis. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the master regulator of oxidative stress, melatonin an endogenous hormone with antioxidative properties that reduces its levels ageing. We have designed new compound combines effects Nrf2 induction properties, idea achieving...
Massive intravascular hemolysis is associated with acute kidney injury (AKI). Nuclear factor erythroid-2-related 2 (Nrf2) plays a central role in the defense against oxidative stress by activating expression of antioxidant proteins. We investigated Nrf2 and whether activation protected hemoglobin (Hb)/heme-mediated renal damage vivo vitro. observed human an experimental model promoted phenylhydrazine intraperitoneal injection. In wild-type mice, Hb/heme released from AKI, resulting decreased...