Repurposing of Tranilast for Potential Neuropathic Pain Treatment by Inhibition of Sepiapterin Reductase in the BH4 Pathway was written by Moore, Benjamin J. R.;Islam, Barira;Ward, Sean;Jackson, Olivia;Armitage, Rebecca;Blackburn, Jack;Haider, Shozeb;McHugh, Patrick C.. And the article was included in ACS Omega in 2019.Reference of 53902-12-8 This article mentions the following:
Tetrahydrobiopterin (BH4) is a cofactor in the production of various signaling mols. including nitric oxide, dopamine, adrenaline, and noradrenaline. BH4 levels are critical for processes associated with cardiovascular function, inflammation, mood, pain, and neurotransmission. Increasing pieces of evidence suggest that BH4 is upregulated in chronic pain. Sepiapterin reductase (SPR) catalyzes both the reversible reduction of sepiapterin to dihydrobiopterin (BH2) and 6-pyruvoyl-tetrahydrobiopterin to BH4 within the BH4 pathway. Therefore, inhibition of SPR by small mols. can be used to control BH4 production and ultimately alleviate chronic pain. Here, we have used various in silico and in vitro experiments to show that tranilast, licensed for use in bronchial asthma, can inhibit sepiapterin reduction by SPR. Docking and mol. dynamics simulations suggest that tranilast can bind to human SPR (hSPR) at the same site as sepiapterin including S157, one of the catalytic triad residues of hSPR. Colorimetric assays revealed that tranilast was nearly twice as potent as the known hSPR inhibitor, N-acetyl serotonin. Tranilast was able to inhibit hSPR activity both intracellularly and extracellularly in live cells. Triple quad mass spectrophotometry of cell lysates showed a proportional decrease of BH4 in cells treated with tranilast. Our results suggest that tranilast can act as a potent hSPR inhibitor and therefore is a valid candidate for drug repurposing in the treatment of chronic pain. In the experiment, the researchers used many compounds, for example, 2-(3-(3,4-Dimethoxyphenyl)acrylamido)benzoic acid (cas: 53902-12-8Reference of 53902-12-8).
2-(3-(3,4-Dimethoxyphenyl)acrylamido)benzoic acid (cas: 53902-12-8) belongs to amides. The amide group is called a peptide bond when it is part of the main chain of a protein, and an isopeptide bond when it occurs in a side chain, such as in the amino acids asparagine and glutamine. Amides can be recrystallised from large quantities of water, ethanol, ethanol/ether, aqueous ethanol, chloroform/toluene, chloroform or acetic acid. The likely impurities are the parent acids or the alkyl esters from which they have been made. The former can be removed by thorough washing with aqueous ammonia followed by recrystallisation, whereas elimination of the latter is by trituration or recrystallisation from an organic solvent.Reference of 53902-12-8
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics