• Bulletin of the Korean Chemical Society
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• v.28 no.2
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• pp.225-228
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• 2007

Lipoic acid (LA) is a multifunctional antioxidant against a variety of ROS. Nitrone acts as free radical spin trap and exhibits neuroprotective activity. Thus, LA-nitrone derivatives (6, 7, 8, and 9) were synthesized and screened as an antioxidant and inhibitors for cholinesterases. Even though the antioxidant effect of LA-nitrone derivatives was not improved, they turned out to be effective inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in μM range.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.4
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• pp.427-433
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• 1998

In brain hypoxic-ischemia, an excess release of glutamate and a marked production of reactive oxygen species (ROS) occur in neuronal and non-neuronal cells. The present study investigated the effect of the biological antioxidants dihydrolipoic acid (DHLA) and lipoic acid (LA) on N-methyl-D-aspartate (NMDA)- and ROS-induced neurotoxicity in cultured rat cortical neurons. DHLA enhanced NMDA-evoked rises in intracellular calcium concentration ($[Ca^{2+}]_i$). In contrast, LA did not alter the NMDA-evoked calcium responses but decreased after a brief treatment of dithiothreitol (DTT), which possesses a strong reducing potential. Despite the modulation of NMDA receptor-mediated rises in $[Ca^{2+}]_i$, neither DHLA nor LA altered the NMDA receptor-mediated neurotoxicity, as assessed by measuring the amount of lactate dehydrogenase released from dead or injured cells. DHLA, but not LA, prevented the neurotoxicity induced by xanthine/xanthine oxidase-generated superoxide radicals. Both DHLA and LA decreased the glutathione depletion-induced neurotoxicity. The present data may indicate that biological antioxidants DHLA and LA protect neurons from ischemic injuries via scavenging oxygen free radicals rather than modulating the redox modulatory site(s) of NMDA receptor.

• Bulletin of the Korean Chemical Society
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• v.32 no.spc8
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• pp.2997-3002
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• 2011

A series of hybrid molecules between (R)-lipoic acid (ALA) and the acetylated or methylated polyphenol compounds were synthesized and their in vitro cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibition activities were checked. The $IC_{50}$ values of all hybrid molecules for a BuChE inhibition were lower than those of the single parent compounds. Specifically, ALA-acetyl protected caffeic acid (11, ALA-AcCA) was shown as an effective inhibitor of BuChE ($IC_{50}=0.5{\pm}0.2\;{\mu}M$) and also had a great selectivity for BuChE over AChE (more than 800 fold). Inhibition kinetic study indicated that 11 is a mixed inhibition type. Its binding affinity ($K_i$) value to BuChE is $1.52{\pm}0.18\;{\mu}M$.

• Journal of Embryo Transfer
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• v.32 no.4
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• pp.267-274
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• 2017

Alpha lipoic acid (ALA) is a biological membranes compound. As the antioxidant, it decreases the oxidized forms of other antioxidant substances such as vitamin C, vitamin E, and glutathione (GSH). To examine the effect of ALA on the in vitro maturation (IVM) of porcine oocytes, we investigated intracellular GSH and reactive oxygen species (ROS) levels, and subsequent embryonic development after parthenogenetic activation (PA). Intracellular GSH levels in oocytes treated with 50uM ALA increased significantly (P < 0.05) and exhibited a significant (P < 0.05) decrease in intracellular ROS levels compared with the control group. Oocytes matured with 50 uM of ALA during IVM displayed significantly higher cleavage rates (67.8% vs. 83.4%, respectively), and higher blastocyst formation rates and total cell number of blastocysts after PA (31.6%, 58.49 vs. 46.8%, 68.58, respectively) than the control group. In conclusion, these results suggest that treatment with ALA during IVM improves the cytoplasmic maturation of porcine oocytes by increasing the intracellular GSH levels, thereby decreasing the intracellular ROS levels and subsequent embryonic developmental potential of PA.

• Bulletin of the Korean Chemical Society
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• v.34 no.11
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• pp.3322-3326
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• 2013

A series of hybrid molecules between (${\alpha}$)-lipoic acid (ALA) and benzyl piperazines were synthesized and their in vitro cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibitory activities were evaluated. Even though the parent compounds did not show any inhibitory activity against cholinesterase (ChE), all hybrid molecules showed BuChE inhibitory activity. Some hybrid compounds also displayed AChE inhibitory activity. Specifically, ALA-1-(3-methylbenzyl)piperazine (15) was shown to be an effective inhibitor of both BuChE ($IC_{50}=2.3{\pm}0.7{\mu}M$) and AChE ($IC_{50}=30.31{\pm}0.64{\mu}M$). An inhibition kinetic study using compound 15 indicated a mixed inhibition type. Its binding affinity ($K_i$) value to BuChE is $2.91{\pm}0.15{\mu}M$.

• Journal of Chest Surgery
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• v.46 no.2
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• pp.162-163
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• 2013

• Polymer(Korea)
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• v.30 no.4
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• pp.357-361
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• 2006

Alpha-lipoic acid (ALA) synthesized in the body has virtues such as anti-oxidation, blood sugar regulation, appetite suppression, and anti-obesity, etc. ALA, which is also used as a drug, has a five-membered ring including disulfide and so easily losses bioavailability due to ring opening and subsequent polymerization by heat or ultraviolet. This report studies various conditions for ring opening polymerization. The ring opening starts above the melting point of ALA, but there was no temperature dependence above it. At $70^{\circ}C$, the degree of ring opening was proportional to reaction time and inversely proportional concentration. The degree of ring opening in acetic acid with UV for 1 hour reached the maximum conversion (70%). Most cleaved ALA changed into disulfide polymers, and the molecular weight of the polymers increased as the amount of ring opening increased.

• Bulletin of the Korean Chemical Society
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• v.34 no.4
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• pp.1025-1029
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• 2013

In the previous paper (Bull. Korean Chem. Soc., 2011, 32, 2997), the hybrid molecules between ${\alpha}$-lipoic acid (ALA) and polyphenols (PPs) connected with neutral 2-(2-aminoethoxy)ethanol linker (linker-1) showed new biological activity such as butyrylcholinesterase (BuChE) inhibition. In order to increase the binding affinity of the hybrid compounds to cholinesterase (ChE), the neutral 2-(2-aminoethoxy)ethanol (linker 1) was switched to the cationic 2-(piperazin-1-yl)ethanol linker (linker 2). The $IC_{50}$ values of the linker-2 hybrid molecules for BuChE inhibition were lower than those of linker-1 hybrid molecules (except 9-2) and they also had the same great selectivity for BuChE over AChE (> 800 fold) as linker-1 hybrid molecules. ALA-acetyl caffeic acid (10-2, ALA-AcCA) was shown as an effective inhibitor of BuChE ($IC_{50}=0.44{\pm}0.24{\mu}M$). A kinetic study using 7-2 showed that it is the same mixed type inhibition as 7-1. Its inhibition constant (Ki) to BuChE is $4.3{\pm}0.09{\mu}M$.

• 한국약용작물학회:학술대회논문집
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• 2008.11a
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• pp.372-373
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• 2008

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.82.1-82.1
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• 2003

The protective adaptive response to electrophiles and reactive oxygen species is mediated by enhanced expression of phase II detoxifying genes including glutathione S-transferases. ${\alpha}$-Lipoic acid, which exerts prooxidant or antioxidant activities, has been shown to activate the insulin signaling pathway and thus to induce insulin-like actions via PI3-kinase and Akt. Our previous studies have shown that PI3-kinase plays an essential role in Nrf2-or C/EBP${\beta}$-mediated glutathione S-transferase A2 (GSTA2) induction. (omitted)