title: Transnitrosation of alicyclic N-nitrosamines containing a sulfur atom.
abstract: Aromatic and aliphatic nitrosamines are known to transfer a nitrosonium ion to another amine. The transnitrosation of alicyclic N-nitroso compounds generates S-nitrosothiols, which are potential nitric oxide donors in vivo. In this study, certain alicyclic N-nitroso compounds based on non-mutagenic N-nitrosoproline or N-nitrosothioproline were synthesised, and the formation of S-nitrosoglutathione (GSNO) was quantified under acidic conditions. We then investigated the effect of a sulfur atom as the substituent and as a ring component on the GSNO formation. In the presence of thiourea under acidic conditions, GSNO was formed from N-nitrosoproline and glutathione, and an N-nitroso compound containing a sulfur atom and glutathione produced GSNO without thiourea. The quantity of GSNO derived from the reaction of the N-nitrosamines containing a sulfur atom and glutathione was higher than that from the N-nitrosoproline and glutathione plus thiourea. Among the analogues that contained a sulfur atom either in the ring or as a substituent, the thiazolidines produced a slightly higher quantity of GSNO than the analogue with a thioamide group. A compound containing sulfur atoms both in the ring and as a substituent exhibited the highest activity for GSNO formation among the alicyclic N-nitrosamines tested. The results indicate that the intramolecular sulfur atom plays an important role in the transnitrosation via alicyclic N-nitroso compounds to form GSNO.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, Yamazaki 2641, Noda-shi, Chiba 278-8510, Japan; Kyoritsu University of Pharmacy, Shibakoen 1-5-30, Minato-ku, Tokyo 105-8512, Japan. Electronic address: inami@rs.noda.tus.ac.jp.
authors.forename: Keiko
authors.initials: K
authors.lastname: Inami
authors.forename: Sonoe
authors.initials: S
authors.lastname: Kondo
authors.forename: Yuta
authors.initials: Y
authors.lastname: Ono
authors.forename: Chiharu
authors.initials: C
authors.lastname: Saso
authors.forename: Masataka
authors.initials: M
authors.lastname: Mochizuki
mesh_terms: D015394:Molecular Structure; D009602:Nitrosamines / Q000737:chemistry*; D026422:S-Nitrosoglutathione / Q000138:chemical synthesis / Q000737:chemistry; D013455:Sulfur / Q000737:chemistry*
chemical_list: D009602:Nitrosamines; D026422:S-Nitrosoglutathione; D013455:Sulfur
keywords: Alicyclic N-nitrosamine; N-Nitrosoproline; N-Nitrosothioproline; S-Nitrosoglutathione; Transnitrosation