A5066831380- Cholinesterase and Neurodegenerative Diseases
- Genomics, phytochemicals, and oxidative stress
- Chemical Synthesis and Analysis
- Synthesis and Biological Evaluation
- Free Radicals and Antioxidants
- Multicomponent Synthesis of Heterocycles
- Biochemical Acid Research Studies
- Synthesis and Characterization of Pyrroles
- Synthesis and Characterization of Heterocyclic Compounds
- Tryptophan and brain disorders
- Piperaceae Chemical and Biological Studies
- Alzheimer's disease research and treatments
- Coenzyme Q10 studies and effects
- Synthesis and biological activity
- Cancer Mechanisms and Therapy
- Axial and Atropisomeric Chirality Synthesis
- Nanomaterials for catalytic reactions
- Synthesis and Reactions of Organic Compounds
- Synthesis and Reactivity of Heterocycles
- Chemical Reaction Mechanisms
- Microtubule and mitosis dynamics
- Drug Solubulity and Delivery Systems
- Synthesis and bioactivity of alkaloids
- HIV Research and Treatment
- Trace Elements in Health
Universidad Complutense de Madrid
2016-2025
Instituto de Ciências Farmacêuticas
2025
Universidade de Santiago de Compostela
2014
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...
Multi-target drug discovery is one of the most active fields in search for new drugs against Alzheimer's disease (AD). This because complexity AD pathological network might be adequately tackled by multi-target-directed ligands (MTDLs) aimed at modulating simultaneously multiple targets such a network. In continuation our efforts to develop MTDLs AD, we have been focusing on molecular hybridization acetylcholinesterase inhibitor tacrine with aim expanding its anti-AD profile. Herein,...
The use of cyclodextrins as drug nano-carrier systems for delivery is gaining importance in the pharmaceutical industry due to interesting pharmacokinetic properties resulting inclusion complexes. In present work, complexes anti-cancer alkaloids camptothecin and luotonin A have been prepared with β-cyclodextrin hydroxypropyl-β-cyclodextrin. These cyclodextrin were characterized by nuclear magnetic resonance spectroscopy (NMR). variations 1H-NMR 13C-NMR chemical shifts allowed establish modes...
Parkinson's disease (PD), the second most common neurodegenerative disorder, affects around 10 million people worldwide. It is a multifactorial marked by dopaminergic neuron loss with oxidative stress (OS) and neuroinflammation as key pathological drivers. Current treatments focus on dopamine replacement are symptomatic, underscoring urgent need for disease-modifying therapies. Here, we present novel class of dual MAO-B inhibitors NRF2 inducers neuroprotective properties in vitro PD models....
The combination of two multicomponent reactions,<italic>i.e.</italic>a Hantzsch-type synthesis 2-pyrrolin-5-ones and a 1,3-dipolar cycloaddition generated complex spirocyclic systems.
Oxidative stress is crucial to the outbreak and advancement of neurodegenerative diseases a common factor many them. We describe synthesis library derivatives 4-arylmethylen-2-pyrrolin-5-one framework by sequential application three-component reaction primary amines, β-dicarbonyl compounds, α-haloketones Knoevenagel condensation. These compounds can be viewed as cyclic amides caffeic ferulic acids, are also structurally related bisavenanthramide family natural antioxidants. Most members...
Curcumin shows a broad spectrum of activities relevance in the treatment Alzheimer's disease (AD); however, it is poorly absorbed and also chemically metabolically unstable, leading to very low oral bioavailability. A small library hybrid compounds designed as curcumin analogues incorporating key structural fragment piperlongumine, natural neuroinflammation inhibitor, were synthesized by two-step route that combines three-component reaction between primary amines, β-ketoesters α-haloesters...
The environmental presence of anions natural origin or anthropogenic is gradually increasing. As a tool to tackle this problem, carbazole derivatives are an attractive gateway the development luminescent chemosensors. Considering different mechanisms proposed for anion recognition, fluorescence properties and anion-binding response several newly synthesised were studied. Potential sensors designed so that they combined native with hydrogen bonding donor groups in critical positions...
Prion diseases are characterized by the self-assembly of pathogenic misfolded scrapie isoforms (PrPSc) cellular prion protein (PrPC). In an effort to achieve a theranostic profile, symmetrical bifunctional carbazole derivatives were designed as fluorescent rigid analogues GN8, pharmacological chaperone that stabilizes native PrPC conformation and prevents its conversion. A focused library was synthesized via four-step route, representative member confirmed have fluorescence, including band...
Abstract Two multitarget hybrids, derived from an aza‐analogue of CGP37157, a mitochondrial Na + /Ca 2+ exchanger antagonist, and lipoic acid were designed in order to combine single molecule the antioxidant Nrf2 induction properties neuroprotective activity CGP37157. The hybrid derivatives showed radical scavenging properties, leading good profile against oxidative stress, together with interesting antineuroinflammatory activity. results obtained show differences depending on configuration...
Hybrids based on an aza-analogue of CGP37157, a mitochondrial Na+/Ca2+ exchanger antagonist, and lipoic acid were obtained in order to combine single molecule the antioxidant NRF2 induction properties neuroprotective activity CGP37157. The four possible enantiomers hybrid structure synthesized by using as key step fully diastereoselective reduction induced Ellman's chiral auxiliary. After computational druggability studies that predicted good ADME profiles blood-brain permeation for all...
Abstract An integrated multidisciplinary approach that combined structure‐based drug design, multicomponent reaction synthetic approaches and functional characterization in enzymatic cell assays led to the discovery of new kinesin spindle protein (KSP) inhibitors with antiproliferative activity. A focused library benzimidazoles obtained by a Ugi+Boc removal/cyclization sequence generated low‐micromolar‐range KSP as promising anticancer prototypes. The design studies chemotypes were assessed...
A step- and atom-economical protocol allowing the synthesis of 1,4-diazepanes also tetrahydro- decahydro-1,5-benzodiazepines is described. The method proceeds from very simple starting materials such as 1,2-diamines alkyl 3-oxohex-5-enoates can be performed under solvent-free conditions in many instances. key event this process was generation situ an aza-Nazarov reagent its subsequent intramolecular aza-Michael cyclization. An intermolecular version reaction established applied to first...
Treatment of a N-2-pyridyl-β-ketoamide precursor with bromine afforded the first example 3-aryl(α-hydroxy)methylenelimidazo[1,2-a]pyridin-2(3H)-one framework. This transformation proceeded through domino process comprising an initial bromination, cyclization via intramolecular SN reaction, and final keto-enol tautomerism, allows generation fused heterocyclic system installation acyl substituent in single operation.
Abstract New 2‐pyrrolin‐5‐ones (IV) are prepared by Hantzsch—type microwave‐assisted, solvent‐free sequential three‐component reaction of primary amines, β‐carbonyl compounds, and α‐bromoester utilized e.g. as synthetic building blocks in a target‐oriented project for the synthesis compound (VI) that is postulated candidate HIV increase inhibition on basis computational studies.
The microwave-assisted reaction of 2-nitroimidazole with 3-bromophenacyl bromide in the presence potassium carbonate as a base and dimethylformamide solvent afforded 2-(3-bromophenyl)imidazo[2,1-b]oxazole. formation this compound was explained via domino mechanism comprising an initial N-alkylation imidazole substrate, followed by base-promoted deprotonation position adjacent to carbonyl give enolate anion that finally cyclizes intramolecular SNAr reaction, loss nitro group nitrite. Then,...