Alzheimer's disease (AD) represents a global problem, with an estimation of the majority of dementia patients in low- and middle-income countries by 2050. Thus, the development of sustainable drugs has attracted much attention in recent years. In light of this, taking inspiration from the HDAC inhibitor vorinostat (1), we develop the first HDAC inhibitors derived from cashew nut shell liquid (CNSL), an inexpensive agro-food waste material. CNSL derivatives 8 and 9 display a HDAC inhibitory profile similar to 1, together with a more promising safety for 9 compared to 1. Moreover, both compounds and particularly 9 were able to effectively modulate glial cell-induced inflammation and to revert the pro-inflammatory phenotype. All these results demonstrate that the use of inexpensive food waste materials could be successfully applied for the development of accessible and sustainable drug candidates for the treatment of AD.

Biomedical Research Center University Hospital Hradec Kralove 500 00 Hradec Kralove Czech Republic

Department of Neuroscience Laboratory of Prion Biology Scuola Internazionale Superiore di Studi Avanzati Via Bonomea 265 1 34136 Trieste Italy

Department of Pharmaceutical Science University of Milan Via Mangiagalli 25 20133 Milan Italy

Department of Pharmacy and Biotechnology Alma Mater Studiorum University of Bologna Via Belmeloro 6 1 40126 Bologna Italy

Department of Pharmacy Health Sciences Faculty University of Brasília Campus Universitário Darcy Ribeiro 70910 900 Brasília DF Brazil

Institute of Pharmaceutical Sciences University of Freiburg Albertstraße 25 79104 Freiburg im Breisgau Germany

LADETER Catholic University of Brasilia QS 07 Lote 01 EPCT Águas Claras 71966 700 Brasília DF Brazil

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Discovery of sustainable drugs for Alzheimer's disease: cardanol-derived cholinesterase inhibitors with antioxidant and anti-amyloid properties

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