PRENYLATED CURCUMIN ANALOGUES AS MULTIPOTENT TOOLS TO TACKLE ALZHEIMER'S DISEASE

Alzheimer's disease is likely to be caused by copathogenic factors including aggregation of A\u3b2 peptides into oligomers and fibrils, neuroinflammation and oxidative stress. To date, no effective treatments are available and because of the multifactorial nature of the disease, it emerges the need to act on different and simultaneous fronts. Despite the multiple biological activities ascribed to curcumin as neuroprotector, its poor bioavailability and toxicity limit the success in clinical outcomes. To tackle Alzheimer's disease on these aspects, the curcumin template was suitably modified and a small set of analogues was attained. In particular, derivative 1 turned out to be less toxic than curcumin. As evidenced by capillary electrophoresis and transmission electron microscopy studies, 1 proved to inhibit the formation of large toxic A\u3b2 oligomers, by shifting the equilibrium towards smaller non-toxic assemblies and to limit the formation of insoluble fibrils. These findings were supported by molecular docking and steered molecular dynamics simulations which confirmed the superior capacity of 1 to bind A\u3b2 structures of different complexity. Remarkably, 1 also showed in vitro anti-inflammatory and anti-oxidant properties. In summary, the curcumin-based analogue 1 emerged as multipotent compound worth to be further investigated and exploited in the Alzheimer's disease multi-target context

An enantioselective imprinted receptor for Z-glutamate exhibiting a binding induced color change

New MIP for the specific recongnition of oxyanions and in particular of dihydrofolate reductase inhibitors such as methotrexate. The strong binding is detected by a colour change and this advocates applications in the field of sensors for the recognition of molecules of pharmaceutical interest. The recognition of oxyanions can also be exploited for the selective analysis of peptides and proteins such as biopharmaceuticals. Nuovo polimero per l’analisi qualitativa (riconoscimento specifico) di ossianioni, in particolare di inibitori della diidrofolatoreduttasi come il metotrexato. La presenza di legame forte, dovuto ad una interazione stechiometrica monomero-templato, è visibile ad occhio nudo (intenso colore giallo) fenomeno interessante applicazioni nel campo dei sensori per molecole di interesse farmaceutico. Si preconizza di estendere l’uso di tale polimero anche nel riconoscimento di molecole di interesse biologico (peptidi, piccole proteine) che contengono la funzione ossianionica

Glucuronide directed molecularly imprinted solid-phase extraction: isolation of testosterone glucuronide from its parent drug in urine

Solid phase extraction (SPE) from urine by using SPE material (molecularly imprinted polymer (MIP) specifically synthesized to recognize and extract testosterone and testosterone glucuronide. Qualitative and quantitative HPLC analysis of testosterone and its metabolite. Estrazione in fase solida (SPE) da urine di sostanza avente attività biologica e tossicologica (testosterone) mediante materiale per SPE altamente specifico, sintetizzato e progettato allo scopo; successiva analisi quali-quantitativa del testosterone e suo metabolita (glucuronide

Synthesis and chromatographic evaluation of molecularly imprinted polymers prepared by the substructure approach for the class-selective recognition of glucuronides

Synthesis of molecularly imprinted polymers (MIPs) to be used as SPE material for the specific extraction of glucuronides. Application to cotinine, mycophenolic acid and testosterone glucuronides. Sintesi di materiale per SPE altamente specifico per il riconoscimento (analisi qualitativa) e quantitativa di metaboliti (glucuronidi) di sostanze aventi attività biologica o tossicologica (cotinina, acido micofenolico, testosterone