Network-Based Drug Optimization toward the Treatment of Parkinson's Disease: NRF2, MAO-B, Oxidative Stress, and Chronic Neuroinflammation.

Parkinson's disease (PD), the second most common neurodegenerative disorder, affects around 10 million people worldwide. It is a multifactorial disease marked by dopaminergic neuron loss with oxidative stress (OS) and neuroinflammation as key pathological drivers. Current treatments focus on dopamine replacement and are symptomatic, underscoring the urgent need for disease-modifying therapies.

Unlocking the Potential of Deep Eutectic Solvents and Ligand-to-Metal Charge Transfer Processes: A Reusable Iron-and-UV-Based System for Sustainable C-C Bond Formation.

Catalytic C-H functionalization has provided new opportunities to access novel organic molecules more sustainably and efficiently. However, these procedures typically rely on precious metals or complex organic catalysts as well as on hazardous solvents or reaction conditions. Herein, a pioneering methodology for direct C-C bond formation enabled by Ligand-to-Metal Charge Transfer (LMCT) and mediated by UV irradiation has been developed using Deep Eutectic Solvents (DESs) as sustainable reaction media.

Quinones as Neuroprotective Agents.

Quinones can in principle be viewed as a double-edged sword in the treatment of neurodegenerative diseases, since they are often cytoprotective but can also be cytotoxic due to covalent and redox modification of biomolecules. Nevertheless, low doses of moderately electrophilic quinones are generally cytoprotective, mainly due to their ability to activate the Keap1/Nrf2 pathway and thus induce the expression of detoxifying enzymes. Some natural quinones have relevant roles in important physiological processes.

Quinolinetrione-tacrine hybrids as multi-target-directed ligands against Alzheimer's disease.

Multi-target drug discovery is one of the most active fields in the search for new drugs against Alzheimer's disease (AD). This is because the complexity of AD pathological network might be adequately tackled by multi-target-directed ligands (MTDLs) aimed at modulating simultaneously multiple targets of such a network. In a continuation of our efforts to develop MTDLs for AD, we have been focusing on the molecular hybridization of the acetylcholinesterase inhibitor tacrine with the aim of expanding its anti-AD profile.

Bifunctional carbazole derivatives for simultaneous therapy and fluorescence imaging in prion disease murine cell models.

Prion diseases are characterized by the self-assembly of pathogenic misfolded scrapie isoforms (PrP) of the cellular prion protein (PrP). In an effort to achieve a theranostic profile, symmetrical bifunctional carbazole derivatives were designed as fluorescent rigid analogues of GN8, a pharmacological chaperone that stabilizes the native PrP conformation and prevents its pathogenic conversion. A focused library was synthesized via a four-step route, and a representative member was confirmed to have native fluorescence, including a band in the near-infrared region.