Francesco Leonetti

Herein, an amperometric fructose biosensor is developed by immobilizing fructose dehydrogenase (FDH) on highly porous gold (h‐PG) electrodes modified with polymeric interlayers. Poly(acrylic acid) (PAA), poly(vinyl alcohol) (PVA), and poly(diallyldimethylammonium chloride) (PDDA) are used to tune the enzyme–electrode interface, generating h‐PG/PAA/FDH, h‐PG/PVA/FDH, and h‐PG/PDDA/FDH bioelectrodes. The h‐PG layer, prepared by hydrogen‐bubble‐assisted electrodeposition, exhibits 18–46 µm pores, nanocoral‐like Au features, and an electroactive area of 26 ± 3 cm ² , about 300 times larger than bare Au. SEM, cyclic voltammetry, and XPS confirm the porous morphology and polymer deposition. The polymer interface controls FDH bioelectrocatalysis. h‐PG/PAA/FDH shows the lowest fructose oxidation onset potential, −0.063 ± 0.005 V, and the highest catalytic current, 32 ± 4 µA at +0.205 V with 10 mM D‐fructose. Amperometry provides a 0.02–1 mM linear range, K _M ^app = 6.4 ± 0.8 mM, sensitivity of 6.4 ± 0.2 µA mM ⁻¹ , and LOD of 5 µM. h‐PG/PAA/FDH retains 95% of its initial response after 180 days in fermentation broth and enables fructose monitoring during Gluconobacter oxydans cultivation. These results identify PAA as the most effective interlayer among those investigated for FDH stabilization, direct electron transfer, and lower onset potential ( E _onset ) for fructose sensing in complex fermentation broth matrices.

Proteolysis-Targeting Chimeras (PROTACs) are heterobifunctional molecules that induce the selective degradation of a protein of interest by recruiting an E3 ubiquitin ligase, thereby triggering ubiquitination and proteasomal clearance. As part of the broader targeted protein degradation (TPD) paradigm, PROTACs offer a powerful strategy to eliminate pathogenic proteins that are difficult to modulate with traditional occupancy-based inhibitors. However, their clinical translation is often limited by poor aqueous solubility, suboptimal cellular permeability, and off-target effects. Notably, some PROTACs retain potent biological activity despite limited membrane permeability, owing to their catalytic mechanism of action, which allows even a small number of molecules reaching the target site to drive substantial protein degradation and produce important pharmacological effects. Growing evidence supports the application of PROTAC-based approaches in neurodegenerative diseases, where the selective removal of toxic or misfolded proteins is particularly attractive. This review summarizes recent advances in chemical protein degradation strategies for neurodegenerative disorders and highlights potential future perspectives of multifunctional PROTACs for therapeutic development.

Alzheimer’s disease (AD) causes a great socioeconomic burden because of its increasing prevalence and the lack of effective therapies. The multifactorial nature of AD prompts researchers to search for new strategies for discovering disease-modifying therapeutics. To this extent, the multitarget approach holds the potential of synergic or cooperative activities arising from compounds that are properly designed to address two or more pathogenetic mechanisms. As a privileged and nature-friendly scaffold, coumarin has successfully been enrolled as the heterocyclic core in the design of multipotent anti-Alzheimer’s agents. Herein, we comprehensively summarize the most recent literature (2018–2023), covering the rational design and the discovery of coumarin-containing multitarget directed ligands (MTDLs) whose anti-AD profile encompassed at least two different biological activities relevant for disease onset and progression. To enhance the clarity of presentation, synthetic coumarin-based MTDLs are categorized into four clusters based on their substitution pattern and reported bioactivities: (i) mono-, (ii) di-, and (iii) polysubstituted coumarins directed at protein targets, and (iv) coumarins directed at protein targets with additional metal-chelating features. Before discussing multimodal coumarins, the rationale for addressing each biological target is briefly presented.

Alzheimer’s disease (AD) exerts a great socioeconomic burden, because of its increasing prevalence and the lack of effective therapies. The multifactorial nature of AD prompted researchers to search for new strategies for discovering disease-modifying therapeutics. To this extent, the multitarget approach holds the potential of synergic or cooperative activities arising from compounds properly designed to address two or more pathogenetic mechanisms. As a privileged and nature-friendly scaffold, coumarin has successfully been enrolled as the heterocyclic core for designing multipotent anti-Alzheimer’s agents. Herein, we summarized the most recent literature (2018-2023) covering the rational design and the discovery of coumarin-containing multitarget directed ligands (MTDLs) whose anti-AD profile encompassed at least two different biological activities relevant for disease onset and progression. To enhance the clarity of presentation, coumarin-based MTDLs are categorized into four clusters based on their substitution pattern and reported bioactivities: i) mono-, ii) di-, and iii) poly-substituted coumarins directed to protein targets; iv) coumarins directed to protein targets with additional metal-chelating features. Before discussing multimodal coumarins, the rationale for addressing each biological target has been briefly presented.

People affected by COVID-19 are exposed to, among others, abnormal clotting and endothelial dysfunction, which may result in deep vein thrombosis, cerebrovascular disorders, and ischemic and non-ischemic heart diseases, to mention a few. Treatments for COVID-19 include antiplatelet (e.g., aspirin, clopidogrel) and anticoagulant agents, but their impact on morbidity and mortality has not been proven. In addition, due to viremia-associated interconnected prothrombotic and proinflammatory events, anti-inflammatory drugs have also been investigated for their ability to mitigate against immune dysregulation due to the cytokine storm. By retrieving patent literature published in the last two years, small molecules patented for long-COVID-related blood clotting and hematological complications are herein examined, along with supporting evidence from preclinical and clinical studies. An overview of the main features and therapeutic potentials of small molecules is provided for the thromboxane receptor antagonist ramatroban, the pan-caspase inhibitor emricasan, and the sodium–hydrogen antiporter 1 (NHE-1) inhibitor rimeporide, as well as natural polyphenolic compounds.

We conducted a monocentric observational study aimed at evaluating the vaccine safety and the pharmaceutical service provided at a community pharmacy (C.PHARM) in the Puglia Region in the period from 29 December 2021 to 12 March 2022 using data from 550 patients of various ages and sexes and with concomitant diseases. We collected anamnestic data, the number of hospitalizations, and any post-vaccination adverse reactions. Interviews using the integrated EQ5 method were also performed to evaluate the quality of the service offered and any therapy preference. As expected, the vaccines were reactogenic after the first dose in the patients with mild–moderate reactions, with younger age and female gender as risk factors. Immune-allergic reactions of a moderate–severe degree were observed in adult females. In the elderly, the vaccination was well tolerated. Comirnaty^® showed a favorable O.R. < 1 vs. other vaccines. No cardiovascular events or hospitalizations were observed up to May 2023. Regional data indicate that all treatments during May 2023 were correlated with the viremia. Paxlovid^TM was prescribed in 3% of the patients in our center and in 1.46% in the region, and distributed/dispensed on behalf of third parties in accordance with a novel distribution/dispensation protocol of the C.PHARM that resulted in a safe vaccination center providing appropriate patient inclusion during vaccination.

We conducted a monocentric observational study aimed at evaluating the pharmaceutical service provided at a Community Pharmacy (C.PH.) during pandemia in our Puglia Region in the period from 29.12.2021 to 12.03.2022 on 550 patients of various ages, sexes, and with concomitant diseases. We collected anamnestic data and any post-vaccination adverse reactions. Interviews with the integrated EQ5 method on evaluating the quality of the service offered and any therapy preference were also performed. As expected, the vaccines were reactogenic after the first dose in the patients with mild-moderate reactions with younger age and female gender as risk factors. Immune-allergic reactions of moderate-severe degree were observed in adult females. In the elderly, the vaccination procedure was well tolerated. Comirnaty showed a favorable O.R.<;1 vs other vaccines. No myocarditis and thromboembolic events in our population were observed. All treatments in May 2023 were correlated with a viremia trend, Paxlovid was prescribed in 3% of the patients in our center and in 1.46% in the Puglia Region with no effects in the hospitalization. It was distributed/dispensed by a novel on behalf of third parties distribution/dispensation (D.P.C.) protocol by the C.PH. The C.PH. resulted in a safe vaccination center providing appropriate patient inclusion during vaccination.

Multicomponent reactions (MCRs) have emerged as a powerful strategy in synthetic organic chemistry due to their widespread applications in drug discovery and development. MCRs are flexible transformations in which three or more substrates react to form structurally complex products with high atomic efficiency. They are being increasingly appreciated as a highly exploratory and evolutionary tool by the medicinal chemistry community, opening the door to more sustainable, cost-effective and rapid synthesis of biologically active molecules. In recent years, MCR-based synthetic strategies have found extensive application in the field of drug discovery, and several anticancer drugs have been synthesized through MCRs. In this review, we present an overview of representative and recent literature examples documenting different approaches and applications of MCRs in the development of new anticancer drugs.