title: Effect of alkyl group on transnitrosation of N-nitrosothiazolidine thiocarboxamides.
abstract: S-Nitrosoglutathione (GSNO) relaxes vascular smooth muscles, prevents platelet aggregation, and acts as a potential in vivo nitric oxide donor. 3-Nitroso-1,3-thiazolidine-4-thiocarboxamide (1), a N-nitrosothio-proline analogue, exhibited a high GSNO formation activity. In this study, two compounds (2 and 3) based on compound 1 were newly synthesized by introducing either one or two methyl groups onto a nitrogen atom on the thioamide substituent in 1. The pseudo-first-order rate constants (kobs) for the GSNO formation for the reaction between the compound and glutathione followed the order 1>2≒3. Thus, the introduction of a methyl group(s) onto the thioamide group led to a decrease in the transnitrosation activity. On the basis of density functional theoretical calculations, the transnitrosation for the N-nitrosothiazolidine thiocarboxamides was proposed to proceed via a bridged intermediate pathway. Specifically, the protonated compound 1 forms a bridged structure between the nitrogen atom in the nitroso group and two sulfur atoms-one in the ring and the other in the substituent. The bridged intermediate gives rise to a second intermediate in which the nitroso group is bonded to the sulfur atom in the thioamide group. Finally, the nitroso group is transferred to GSH 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, Tokyo, Japan. Electronic address: inami@rs.noda.tus.ac.jp.
authors.forename: Keiko
authors.initials: K
authors.lastname: Inami
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, Yamazaki 2641, Noda-shi, Chiba 278-8510, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Ono
authors.affiliation: Kyoritsu University of Pharmacy, Tokyo, Japan.
authors.forename: Sonoe
authors.initials: S
authors.lastname: Kondo
authors.affiliation: Radio-Redox-Response Research Team, Advanced Particle Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences (NIRS), Inage-ku, Chiba 263-8555, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Nakanishi
authors.affiliation: Department of Material and Life Science, Graduate School of Engineering, Osaka University, ALCA and SENTAN, Japan Science and Technology Agency (JST), Suita, Osaka 565-0871, Japan; Department of Bioinspired Science, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Kei
authors.initials: K
authors.lastname: Ohkubo
authors.affiliation: Department of Material and Life Science, Graduate School of Engineering, Osaka University, ALCA and SENTAN, Japan Science and Technology Agency (JST), Suita, Osaka 565-0871, Japan; Department of Bioinspired Science, Ewha Womans University, Seoul 120-750, Republic of Korea; Faculty of Science and Engineering, Meijo University, ALCA and SENTAN, Japan Science and Technology Agency (JST), Nagoya, Aichi 468-0073, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Fukuzumi
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, Yamazaki 2641, Noda-shi, Chiba 278-8510, Japan; Kyoritsu University of Pharmacy, Tokyo, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Mochizuki
mesh_terms: D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D015394:Molecular Structure; D015538:Nitrosation; D009603:Nitroso Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D011789:Quantum Theory; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry; D053778:Thiazolidines / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D009603:Nitroso Compounds; D013844:Thiazoles; D053778:Thiazolidines; C042199:N-nitrosothiazolidine
keywords: 1,3-Thiazolidine; N-Nitrosothioproline; S-Nitrosoglutathione; Thiocarboxamide; Transnitrosation