Deep Eutectic Solvents as Convenient Media for the Preparation of Semi-synthetic Anti-AD Multi-Target Hybrids

Alzheimer's disease (AD) is the most common neurodegenerative disorder, and its multifactorial origin suggests the possibility of studying multi-target drugs. Particularly intriguing could be using nature as a source of inspiration for the development of new compounds with multiple activities, considering the growing interest in natural medicine and nutraceuticals. Starting from our recent results,2-4 the NInFA project, funded under the PRIN 2022 PNRR call, aims to obtain novel nature-inspired hybrids active on classic and novel AD targets. These molecules are synthesized using a semi-synthetic approach, combining the structures of the fungal secondary metabolites ochratoxin α (OTα) and/or ochratoxin β (OTβ), produced by microfungi, with moieties mimicking current anti-AD drugs, such as donepezil and rivastigmine. One of the innovative goals of this project is the development of more economical and sustainable processes. In particular, the optimization of the synthesis of chemical fragments involves the use of Deep Eutectic Solvents (DESs) in replacement of classical volatile organic compounds (VOCs). In addition, DESs have been employed for the extraction and purification of scaffolds produced by liquid fungal cultures, with the aim to make the whole process completely eco-friendly.