Multifunctional Lipoic Acid Conjugates

Abstract

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.

Phytosterol and α-Lipoic Acid Conjugates: Synthesis, Free Radical Scavenging Capacity and RP-LC-MS-APCI Analysis

“…Improved solubility promotes more uniform formulation which is important for consistent cholesterol reducing effects, even though free PS and PS es- Conjugates of LA have been synthesised for their anticipated dual and/or synergistic health benefi ts. In addition, it has been suggested that LA conjugates may possess its therapeutic effect at lower concentrations than required for LA alone [Koufaki et al, 2009].…”

“…Preparation of hybrid molecules is a common approach to create effi cient and/or synergistic effects either on single or dual targets. It was also suggested that multifunctional LA conjugates may bring their therapeutic effects at lower concentrations compared to the LA as a single molecule [Koufaki et al, 2009;Melagraki et al, 2009]. The main objectives of this study were to synthesize LA and DHLA conjugates of PS in a mixture (β-sito-, stigma-, campe-, and brassicasterol), yielding phytosterol lipoate (PSLA) and phytosterol dihydrolipoate (PSDHLA), respectively, and to verify them by NMR and HPLC-MS. To our knowledge, no research paper has been published on these conjugates .…”

Two Novel Donepezil-Lipoic Acid Hybrids: Synthesis, Anticholinesterase and Antioxidant Activities and Theoretical Studies

“…26 Thus, LA is a good prototype to design new hybrids to combat AD, and previously developed LA hybrids maintained the antioxidant activity and showed other beneficial activities such as inhibition of AChE and BuChE as well as neuroprotective and anti-inflammatory activity. 27,28 In 2005, Rosini et al 29 reported the synthesis of lipocrine, an LA-tacrine hybrid, which further inspired the development of other hybrids featuring an LA fragment connected with N 1 -ethyl-N 1 -(2-methoxy-benzyl)-hexane-1,6-diamine moiety or with rivastigmine. 26 Although there are works involving the hybridization of the benzyl-piperidine moiety of donepezil with LA, to our knowledge, there is no report on the hybridization of the indanone-piperidine moiety with LA.…”

“…27,28 In 2005, Rosini et al 29 reported the synthesis of lipocrine, an LA-tacrine hybrid, which further inspired the development of other hybrids featuring an LA fragment connected with N 1 -ethyl-N 1 -(2-methoxy-benzyl)-hexane-1,6-diamine moiety or with rivastigmine.…”

A Novel Method of Immobilizing Antigens on Gold Electrode for Immunosensing

“…Many studies paid attention to sulfide and disulfide moiety compounds, with lipoic acid being one of the most useful compounds for gold surface functionalization [2,3]. Lipoic acid was widely used because its alkyl chain length and disulfide attachment c 2015 Vietnam Academy of Science and Technology to gold surface results in the enhanced stability of the monolayer [4,5]. The functionalization of the self-assembled monolayer after activation with a mixture of dicyclohexyl carbodiimide and N-hydroxysuccinimide is a well established method for the further functionalization of biosensors [6].…”