Non-enzymatic reduction of a 1,2,4-thiadiazolium derivative.
It was discovered that 2,3-bis-(2-methoxy-phenyl)-5-phenylamino-[1,2,4]-thiadiazolium bromide (1), a 1,2,4-thiadiazolium derivative, could be reduced to the corresponding imidoylthiourea, 1-[(2-methoxy-phenyl)-(2-methoxy-phenylimino)-methyl]-3-phenyl-thiourea (3), by some biologically interesting reducing reagents including glutathione, cysteine, and ascorbic acid. The reduction also occurred in Sprague-Dawley rat and Yorkshire swine plasma, suggesting that thiol containing biological molecules existing in the plasma are mainly responsible for this reaction. A facile method for preparation of 3 from 1 was established by using 2-thioethanol as reaction reagent as well as solvent. The structure of 3 was fully characterized using nuclear magnetic resonance (NMR) and mass spectrometry with electrospray ionization source (ESI-MS). Those new findings could shed light on the development of 1,2,4-thiadiazolium derivatives for their potential pharmaceutical applications.
Zhang
Fa
F
Analytical Development, Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ 08558, USA. fzhang1@cpcus.jnj.com
Estavillo
Carmelita
C
Mohler
Margie
M
Cai
Jane
J
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization; D013552:Swine; D013890:Thiourea / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification
C529343:1-((2-methoxy-phenyl)-(2-methoxy-phenylimino)methyl)-3-phenyl-thiourea; D000975:Antioxidants; D005978:Glutathione; D013890:Thiourea; D003545:Cysteine; D001205:Ascorbic Acid