Showing papers by "J. Carlos Menéndez published in 2023"

Small-molecule theranostics in Alzheimer's disease.

Abstract: Alzheimer's Disease (AD) remains one of the most challenging health-related issues for our society. It is becoming increasingly prevalent, especially in developed countries, due to the rising life expectancy and, moreover, represents a considerable economic burden worldwide. All efforts at the discovery of new diagnostic and therapeutic tools in the last decades have invariably met with failure, making AD an incurable illness and underscoring the need for new approaches. In recent years, theranostic agents have emerged as an interesting strategy. They are molecules able to simultaneously provide diagnostic information and deliver therapeutic activity, allowing for the assessment of the molecule activity, the organism response and the pharmacokinetics. This makes these compounds promising for streamlining research on AD drugs and for their application in personalized medicine. We review here the field of small-molecule theranostic agents as promising tools for the development of novel diagnostic and therapeutic resources against AD, highlighting the positive and significant impact that theranostics can be expected to have in the near future in clinical practice.

2-(3-Bromophenyl)imidazo[2,1-b]oxazole

Abstract: The microwave-assisted reaction of 2-nitroimidazole with 3-bromophenacyl bromide in the presence of potassium carbonate as a base and dimethylformamide as a solvent afforded 2-(3-bromophenyl)imidazo[2,1-b]oxazole. The formation of this compound was explained via a domino mechanism comprising an initial N-alkylation reaction of the imidazole substrate, followed by the base-promoted deprotonation of the position adjacent to the carbonyl to give an enolate anion that finally cyclizes via an intramolecular SNAr reaction, with the loss of the nitro group as potassium nitrite. Then, the proposed 1-(3-bromophenacyl)-2-nitroimidazole intermediate could be isolated by reducing the reaction time and was shown to be a precursor of the imidazo[2,1-b]oxazole final product.

A New Method for the Introduction of an Acylsulfonamide Moiety Applied to a 3-Substituted Functionalized Indole Framework Related to the Welwitindolinone Alkaloids

Abstract: The one-pot reaction between an  -formylcyclohexanone derivative and tosyl azide in the presence of rhodium trifluoroacetate dimer afforded an acylsulfonamide derivative. This transformation is proposed to arise from a domino mechanism involving the in situ generation, through the Regitz method, of an  -diazoketone, followed by its transformation into a rhodium carbenoid and its combination with N -tosylformamide, generated as a side product of the first step of the mechanism. Overall, this transformation leads to the generation of a C– N bond between the formyl carbon and the azide nitrogen adjacent to the sulfonyl group.

m-Terphenylamines, Acting as Selective COX-1 Inhibitors, Block Microglia Inflammatory Response and Exert Neuroprotective Activity

Abstract: Inhibition of cyclooxygenase-2 (COX-2) has been extensively studied as an approach to reduce proinflammatory markers in acute brain diseases, but the anti-neuroinflammatory role of cyclooxygenase-1 (COX-1) inhibition has been rather neglected. We report that m-terphenylamine derivatives are selective COX-1 inhibitors, able to block microglia inflammatory response and elicit a neuroprotective effect. These compounds were synthesized via a three-component reaction of chalcones, β-ketoesters, and primary amines, followed by hydrolysis/decarboxylation of the ester group. Together with their synthetic intermediates and some urea derivatives, they were studied as inhibitors of COX-1 and COX-2. The m-terphenylamine derivatives, which were selective COX-1 inhibitors, were also analyzed for their ability to block microglia inflammatory and oxidative response. Compound 3b presented an interesting anti-inflammatory and neuroprotective profile by reducing nitrite release, ROS overproduction, and cell death in organotypic hippocampal cultures subjected to LPS. We thus show that COX-1 inhibition is a promising approach to provide enhanced neuroprotection against acute inflammatory processes, which are crucial in the development of a plethora of acute neurodegenerative injuries.