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Several hundreds of studies published the last decade have reported that alpha-lipoic acid (LA) possess the potential to intervene in various therapeutically interesting pathways. However, it should be noted that LA reportedly exerts most of its effects at high micromolar concentrations; that amides of LA exhibit higher biological activity than the parent compound; and that molecular combinations (hybrids) obtained by coupling LA with an amino-substituted bioactive moiety, possess multifunctional activity. The design and synthesis of hybrid molecules encompassing two pharmacophores in one molecular scaffold is a well established approach to the synthesis of more potent drugs with dual activity. Using this approach, various research groups have recently designed and synthesized hybrid compounds with antioxidant activity hyphenated with a wide variety of other activities such as neuroprotective, cardioprotective, anti-inflammatory, antidiabetic and anticancer activity as well as enzyme inhibition. Moreover, LA represents an ideal chemical entity for the development of biologically interesting functionalized nanoparticles. Many recent publications describe the use of LA: i) as component of nanospheres and nanoprodrugs, ii) as a linker for the attachment of lipids, carbohydrates, proteins and oligonucleotides on gold nanoparticles to form Self Assembled Monolayers (SAMs) and iii) as surface ligand for cap exchange reactions to prepare water-soluble semiconducting nanocrystal Quantum Dots (QDs). This review is focused on the growing field of the design and synthesis of LA conjugates, for the development of novel molecules with a dual mode of action and the construction of nanosized antioxidants, Self Assembled Monolayers and Quantum Dots.

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