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.

Graphical abstract2,3-Bis-(2-methoxy-phenyl)-5-phenylamino-[1,2,4]-thiadiazolium bromide (1), a 1,2,4-thiadiazolium derivative, was reduced to the corresponding imidoylthiourea, 1-[(2-methoxy-phenyl)-(2-methoxy-phenylimino)-methyl]-3-phenyl-thiourea (3), by some biological interesting reducing reagents including glutathione, cysteine, and ascorbic acid. The reduction also occurred in Sprague–Dawley rat and Yorkshire swine plasma. Chemical trapping studies suggested 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 a reaction reagent as well as a solvent. Those new findings could shed lights on the development of 1,2,4-thiadiazolium derivatives for their potential pharmaceutical applications.Figure optionsDownload full-size imageDownload as PowerPoint slide