Selective central nervous system (CNS) drug delivery is one of the major challenges in medicinal chemistry. There is a high number of patients suffering from neurodegenerative disorders worldwide and very low efficacy of the reduced arsenal of available treatments. Understanding some of the molecular changes associated to these ubiquitous and widespread diseases has stimulated efforts to develop drugs that specially interact with key targets.<br/>Although the blood brain barrier (BBB) prevents most drugs from reaching their targets in the brain, molecular vectors offer great potential to safely overcome this issue and allow accumulation at the site of action at therapeutic levels. The BBB shuttles that cross this barrier, together with polymers such as polyethylene glycols (PEGs), that already proved to moderately inhibit P-glycoprotein efflux, are presented as promising pieces to construct drug-carriers for improving the effects of different molecules.<sup>[1-3] </sup><br/>Computer-assisted design and synthesis of potent molecules, together with the development of new carriers, allows a wide range of possibilities for targeted therapies. Knowledge on biochemical processes brings the opportunity to provide treatments potentially less toxic and more effective than traditional therapeutic approaches. We report different approaches and illustrate their successful implementation in the search for better treatments for neurodegenerative diseases.

Hybrid molecules for neurodegenerative diseases: From small molecules to brain drug delivery systems

ACS Spring Meeting 2021

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