Dataset Information

Diaminoterephthalate-?-lipoic acid conjugates with fluorinated residues.

ABSTRACT: Two bifunctional diaminoterephthalate (DAT) fluorescence dyes were prepared in a three-step sequence including one deprotection reaction. One functional unit is ?-lipoic acid (ALA) for binding the dye to gold surfaces. It was introduced to the DAT scaffold by an amidation reaction. The other functional unit is a para-(trifluoromethyl)benzyl group for facile detection of the surface-bound material by X-ray photoelectron spectroscopy (XPS). This residue was introduced by reductive amination of the DAT scaffold with the respective benzaldehyde derivative. In one compound (60% yield over three steps) the ALA unit is directly bound to the DAT as a relatively electron-withdrawing amide. In solution (CH₂Cl₂), this material shows strong fluorescence (quantum yield 57% with emission at 495 nm, absorption maximum at 420 nm). The other compound (57% yield over three steps) possesses a propylene spacer between the ALA and the DAT units for electronic decoupling, thus, bathochromic shifts are observed (absorption at 514 nm, emission at 566 nm). The quantum yield is, however, lower (4%). Self-assembled monolayers on a gold surface of both compounds were prepared and characterized by high-resolution XPS of the C 1s, O 1s, S 2p, N 1s and F 1s emissions. The high signal-to-noise ratios of the F 1s peaks indicated that trifluoromethylation is an excellent tool for the detection of surface-bound materials by XPS.

SUBMITTER: Buschbeck L

PROVIDER: S-EPMC6541350 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Diaminoterephthalate-α-lipoic acid conjugates with fluorinated residues.

Buschbeck Leon L Markovic Aleksandra A Wittstock Gunther G Christoffers Jens J

Beilstein journal of organic chemistry 20190426

Two bifunctional diaminoterephthalate (DAT) fluorescence dyes were prepared in a three-step sequence including one deprotection reaction. One functional unit is α-lipoic acid (ALA) for binding the dye to gold surfaces. It was introduced to the DAT scaffold by an amidation reaction. The other functional unit is a <i>para</i>-(trifluoromethyl)benzyl group for facile detection of the surface-bound material by X-ray photoelectron spectroscopy (XPS). This residue was introduced by reductive amination ...[more]

PMID: 31164936

Similar Datasets

Project description:Alzheimer's disease (AD) is a neurodegenerative disorder characterised by impairments in the cognitive domains associated with orientation, recording, and memory. This pathology results from an abnormal deposition of the ?-amyloid (A?) peptide and the intracellular accumulation of neurofibrillary tangles. Mitochondrial dysfunctions play an important role in the pathogenesis of AD, due to disturbances in the bioenergetic properties of cells. To date, the usual therapeutic drugs are limited because of the diversity of cellular routes in AD and the toxic potential of these agents. In this context, alpha-lipoic acid (?-LA) is a well-known fatty acid used as a supplement in several health conditions and diseases, such as periphery neuropathies and neurodegenerative disorders. It is produced in several cell types, eukaryotes, and prokaryotes, showing antioxidant and anti-inflammatory properties. ?-LA acts as an enzymatic cofactor able to regulate metabolism, energy production, and mitochondrial biogenesis. In addition, the antioxidant capacity of ?-LA is associated with two thiol groups that can be oxidised or reduced, prevent excess free radical formation, and act on improvement of mitochondrial performance. Moreover, ?-LA has mechanisms of epigenetic regulation in genes related to the expression of various inflammatory mediators, such PGE2, COX-2, iNOS, TNF-?, IL-1?, and IL-6. Regarding the pharmacokinetic profile, ?-LA has rapid uptake and low bioavailability and the metabolism is primarily hepatic. However, ?-LA has low risk in prolonged use, although its therapeutic potential, interactions with other substances, and adverse reactions have not been well established in clinical trials with populations at higher risk for diseases of aging. Thus, this review aimed to describe the pharmacokinetic profile, bioavailability, therapeutic efficacy, safety, and effects of combined use with centrally acting drugs, as well as report in vitro and in vivo studies that demonstrate the mitochondrial mechanisms of ?-LA involved in AD protection.

Project description:Cisplatin, a small platinum-containing molecule, is a widely used, highly effective anticancer drug. However, severe side effects have been found in cancer patients treated with cisplatin, including nephrotoxicity, neurotoxicity, and ototoxicity. These cisplatin-induced side effects can have a major impact on patient quality of life, including social development problems in pediatric patients that develop hearing loss. Previous studies have suggested that the major cause of cisplatin-induced ototoxicity is abnormal accumulation of reactive oxygen species (ROS) and oxidative stress. Alpha-lipoic acid (ALA), one of the most effective antioxidants, is known to be involved in the cellular antioxidant system and may have a protective effect on cisplatin-induced ototoxicity. However, the therapeutic effect of ALA on damaged hearing function and its detailed mechanism of action are not fully understood. This study focused on determining whether ALA has a potential as a protective and/or therapeutic agent for cisplatin-induced ototoxicity. Histological and physiological analyses were performed using cisplatin-treated mouse cochlea and HEI-OC1 culture cells in pre- and post-treatment with ALA in vitro and in vivo. We found that ALA contributes to protecting mitochondrial function by preventing ROS accumulation and inhibiting apoptotic cell death. Importantly, post-treatment with ALA consistently showed an almost equal restorative effect to pretreatment, in vitro and in vivo, supporting the possible use of ALA as a therapeutic agent for cisplatin-induced ototoxicity. This study is the first report on a strong therapeutic potential of ALA to rescue ototoxic hearing loss caused by cisplatin, and our data provide key evidence that ALA may act as a reducing agent for glutathione disulfide to increase glutathione levels on behalf of glutathione reductase. This result was consistent in both cultured cells and the mouse model, which improves the clinical value of ALA for therapy of cisplatin-induced ototoxicity.

Dataset Information

Diaminoterephthalate-?-lipoic acid conjugates with fluorinated residues.

Publications

Diaminoterephthalate-α-lipoic acid conjugates with fluorinated residues.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets