N-Propargylglycine: a unique suicide inhibitor of proline dehydrogenase with anticancer activity and brain-enhancing mitohormesis properties was written by Scott, Gary K.;Mahoney, Sophia;Scott, Madeleine;Loureiro, Ashley;Lopez-Ramirez, Alejandro;Tanner, John J.;Ellerby, Lisa M.;Benz, Christopher C.. And the article was included in Amino Acids in 2021.Application of 16310-13-7 This article mentions the following:
Proline dehydrogenase (PRODH) is a mitochondrial inner membrane flavoprotein critical for cancer cell survival under stress conditions and newly recognized as a potential target for cancer drug development. Reversible (competitive) and irreversible (suicide) inhibitors of PRODH have been shown in vivo to inhibit cancer cell growth with excellent host tolerance. Surprisingly, the PRODH suicide inhibitor N-propargylglycine (N-PPG) also induces rapid decay of PRODH with concordant upregulation of mitochondrial chaperones (HSP-60, GRP-75) and the inner membrane protease YME1L1, signifying activation of the mitochondrial unfolded protein response (UPRmt) independent of anticancer activity. The present study was undertaken to address two aims: (i) use PRODH overexpressing human cancer cells (ZR-75-1) to confrm the UPRmt inducing properties of N-PPG relative to another equipotent irreversible PRODH inhibitor, thiazolidine-2-carboxylate (T2C); and (ii) employ biochem. and transcriptomic approaches to determine if orally administered N-PPG can penetrate the blood-brain barrier, essential for its future use as a brain cancer therapeutic, and also potentially protect normal brain tissue by inducing mitohormesis. Oral daily treatments of N-PPG produced a dose-dependent decline in brain mitochondrial PRODH protein without detectable impairment in mouse health; furthermore, mice repeatedly dosed with 50 mg/kg N-PPG showed increased brain expression of the mitohormesis associated protease, YME1L1. Whole brain transcriptome (RNAseq) analyses of these mice revealed signifcant gene set enrichment in N-PPG stimulated neural processes (FDR p<0.05). Given this in vivo evidence of brain bioavailability and neural mitohormesis induction, N-PPG appears to be unique among anticancer agents and should be evaluated for repurposing as a pharmaceutical capable of mitigating the proteotoxic mechanisms driving neurodegenerative disorders. In the experiment, the researchers used many compounds, for example, Thiazolidine-2-carboxylic acid (cas: 16310-13-7Application of 16310-13-7).
Thiazolidine-2-carboxylic acid (cas: 16310-13-7) belongs to thiazolidine derivatives. Thiazolidine is an important scaffold and has a wide range of promising biological activities. Thiazolidine derivatives have reported anti-inflammatory and anti-nociceptive activity. Thiazolidine-2,4-dione (TZD) is an important derivative of thiazolidine with a sulfur and nitrogen atom in positions 1 and 3, and carbonyl in position 4 of the ring. These derivatives have a wide range of medicinal applications such as antiviral, antimicrobial, anticonvulsant, antiinflammatory, and antimalarial activities.Application of 16310-13-7
Referemce:
Thiazolidine – Wikipedia,
Thiazolidine – ScienceDirect.com