Cysteine and glutathione mixed-disulfide conjugates of thiosulfinates: chemical synthesis and biological activities.
The chemical syntheses of cysteine (CYS) and glutathione (GSH) mixed -disulfide conjugates (CySSR, GSSR, respectively) of mercapto residues representing most of the R groups of thiosulfinates (R = methyl, ethyl, propyl, and allyl) are described. Gram-scale conjugates were prepared as >98% pure preparations, with 80% reaction yield for each of the two seminal synthesis steps, with structures confirmed by (1)H NMR and high-resolution MS analyses. These conjugates are derivatives of thiosulfinates that may be evolved in processed foods, in the digestive tract, and through in vivo metabolism. The prepared conjugates were found to be able to induce quinone reductase (QR, a representative phase II enzyme) in murine hepatoma cells (Hepa 1c1c7) and to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated macrophage cells (RAW 264.7), indicating they have potential cancer preventive and anti-inflammatory activities. Among the prepared conjugates, the allyl conjugates of CYS and GSH, S-allylmercaptocysteine (CySSA) and S-allylmercaptoglutathione (GSSA), showed the most potent activity regarding QR induction and NO production inhibition. The conjugates with saturated R groups were also active and conferred biological activity as cystine and oxidized glutathione exhibited no effects in these cellular assays.
Zhang
Guodong
G
Department of Food Science, Babcock Hall, University of Wisconsin-Madison, 1605 Linden Drive, Madison, Wisconsin 53706, USA.
Li
Bin
B
Lee
Chen-Hsien
CH
Parkin
Kirk L
KL
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003553:Cystine / Q000737:chemistry* / Q000494:pharmacology; D004220:Disulfides / Q000737:chemistry* / Q000494:pharmacology; D005978:Glutathione / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D013886:Thiosulfonic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D004220:Disulfides; D013886:Thiosulfonic Acids; D009569:Nitric Oxide; D003553:Cystine; D016660:NAD(P)H Dehydrogenase (Quinone); D005978:Glutathione