Thiopurine drugs repositioned as tyrosinase inhibitors was written by Choi, Joonhyeok;Lee, You-Mie;Jee, Jun-Goo. And the article was included in International Journal of Molecular Sciences in 2018.Category: amides-buliding-blocks This article mentions the following:
Drug repositioning is the application of the existing drugs to new uses and has the potential to reduce the time and cost required for the typical drug discovery process. In this study, we repositioned thiopurine drugs used for the treatment of acute leukemia as new tyrosinase inhibitors. Tyrosinase catalyzes two successive oxidations in melanin biosynthesis: the conversions of tyrosine to dihydroxyphenylalanine (DOPA) and DOPA to dopaquinone. Continuous efforts are underway to discover small mol. inhibitors of tyrosinase for therapeutic and cosmetic purposes. Structure-based virtual screening predicted inhibitor candidates from the US Food and Drug Administration (FDA)-approved drugs. Enzyme assays confirmed the thiopurine leukemia drug, thioguanine, as a tyrosinase inhibitor with the inhibitory constant of 52μM. Two other thiopurine drugs, mercaptopurine and azathioprine, were also evaluated for their tyrosinase inhibition; mercaptopurine caused stronger inhibition than thioguanine did, whereas azathioprine was a poor inhibitor. The inhibitory constant of mercaptopurine (16μM) was comparable to that of the well-known inhibitor kojic acid (13μM). The cell-based assay using B16F10 melanoma cells confirmed that the compounds inhibit mammalian tyrosinase. Particularly, 50μM thioguanine reduced the melanin content by 57%, without apparent cytotoxicity. Cheminformatics showed that the thiopurine drugs shared little chem. similarity with the known tyrosinase inhibitors. In the experiment, the researchers used many compounds, for example, 2-(3-(3,4-Dimethoxyphenyl)acrylamido)benzoic acid (cas: 53902-12-8Category: amides-buliding-blocks).
2-(3-(3,4-Dimethoxyphenyl)acrylamido)benzoic acid (cas: 53902-12-8) belongs to amides. Compared to amines, amides are very weak bases and do not have clearly defined acid–base properties in water. On the other hand, amides are much stronger bases than esters, aldehydes, and ketones. 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.Category: amides-buliding-blocks
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics