Biogenic polyamines, especially spermine and spermidine, are associated with cell growth and development. These amines can be found at high concentrations in the tumor cells, tissues, and urine of cancer patients. In contrast, spermidine levels drop with age, and a possible connection between low endogenous spermidine concentrations and age-related deterioration has been suggested. Thus, the quantification of these amines in body fluids like urine could be used in the diagnosis of different pathological situations. Here a new fluorescent molecular probe based on a tetraphenylethylene derivative is reported. This probe is able to selectively detect these amines through the enhancement of the fluorescence emission of the resulting complex. This fluorescence enhancement may be related to restricted intramolecular rotations of TPE phenyl rings induced by the analyte. Theoretical studies were carried out to shed light on the observed selectivity. Finally, the detection of these amines in urine was performed with limits of detection of 0.70 µM and 1.17 µM for spermine and spermidine, respectively.

Alzheimer's disease (AD) is a progressive neurodegenerativedisorder that has no cure because its etiology is still unknown, andits main treatment is the administration of acetylcholinesterase (AChE)inhibitors. The study of the mechanism of action of this family ofcompounds is critical for the design of new more potent and specificinhibitors. In this work, we study the molecular basis of an uncompetitiveinhibitor (compound 1, 2 & beta;, 3 & alpha;-dihydroxy-5 & alpha;-cholestan-6-onedisulfate), which we have proved to be a peripheral anionic site (PAS)-bindingAChE inhibitor. The pipeline designed in this work is key to the developmentof other PAS inhibitors that not only inhibit the esterase actionof the enzyme but could also modulate the non-cholinergic functionsof AChE linked to the process of amylogenesis. Our studies showedthat 1 inhibits the enzyme not simply by blocking themain gate but by an allosteric mechanism. A detailed and careful analysisof the ligand binding position and the protein dynamics, particularlyregarding their secondary gates and active site, was necessary toconclude this. The same analysis was executed with an inactive analogue(compound 2, 2 & beta;, 3 & alpha;-dihydroxy-5 & alpha;-cholestan-6-one).Our first computational results showed no differences in affinityto AChE between both steroids, making further analysis necessary.This work highlights the variables to be considered and develops arefined methodology, for the successful design of new potent dual-actiondrugs for AD, particularly PAS inhibitors, an attractive strategyto combat AD.

Fluorescent labelling is a versatile tool to visualize biomolecules containing primary amines in their cellular environment, allowing the study of their function or interactions. Here, three organic fluorophores that can irreversibly bind to the primary amine group on the target biomolecule are reported. They consist of push–pull heterocyclic dyes based on bithiophene and incorporating a terminal N -hydroxysuccinimidyl ester as a reactive group for labelling primary amine groups from biomolecules as (poly)amines, peptides or proteins. Their potential as chemosensors for primary amines, using N _α -Boc protected amino acid l -lysine as a model, was assessed through UV–Visible, fluorescence and ¹ H NMR titrations.