ArticleJournal of enzyme inhibition and medicinal chemistry2019
Design, synthesis, and biological evaluation of novel derivatives of dithiodiglycolic acid prepared via oxidative coupling of thiols.
Article in Journal of enzyme inhibition and medicinal chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 4 citations in OpenAlex.
- Ru(III) Complexes with Lonidamine-Modified Ligands.International journal of molecular sciences · 2021Article
- Sulfocoumarins as dual inhibitors of human carbonic anhydrase isoforms IX/XII and of human thioredoxin reductase.Journal of enzyme inhibition and medicinal chemistry · 2020Article
- Combining carbonic anhydrase and thioredoxin reductase inhibitory motifs within a single molecule dramatically increases its cytotoxicity.Journal of enzyme inhibition and medicinal chemistry · 2020Article
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Authors and funding
9 authors at 4 institutions in 3 countries.
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No grant is acknowledged in the PubMed record.
Abstract
Human thioredoxin reductase 1 (TrxR1) is a selenocysteine-containing enzyme which plays a crucial role in regulating numerous redox signalling pathways within the cell. While its functioning is important in all cells, levels of TrxR1 expression are higher in cancer cells, possibly as an adaptation to much higher levels of reactive oxygen species and the need for more extensive DNA synthesis. This makes TrxR1 an attractive target for cancer therapy development. Inspired by the structure of disulphide compounds which have advanced through various stages of clinical development, we designed a series of dithiodiglycolic acid derivatives. These were prepared from respective thiol synthons using an iodine- or benzotriazolyl chloride-promoted oxidative disulphide bond formation. Inhibition of TrxR present in cell lysates from human neuroblastoma cells (SH-SY5Y) and rat liver cells indicated several compounds with a potential for TrxR inhibition. Some of these compounds were also tested for growth inhibition against two human cancer cell lines and normal human keratinocytes.
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