Synthesis and biological evaluation of immunosuppressive agent DZ2002 and its stereoisomers

DZ2002 and its related stereoisomers were efficiently synthesized. The optical data of (R)- and (S)-DZ2002 were disclosed here for the first time. Their inhibitory potency was evaluated on SAHase and MLR assay in the mean time. In accordance with respective inhibitory potency of SAHase, the immunosuppressive potency order was demonstrated as (S)-DZ2002 > (Rac)-DZ2002 > (R)-DZ2002 > (Keto)-DZ2002. These results indicate (S)-configuration of 2-chiral center in DZ2002 is important for binding with SAHase.

DZ2002 and its stereoisomers were efficiently prepared and evaluated on their potency against SAHase and mixed lymphocyte reaction (MLR). In accordance with respective inhibitory potency of SAHase, the immunosuppressive potency order was demonstrated as (S)-DZ2002 > (Rac)-DZ2002 > (R)-DZ2002 > (Ketone)-DZ2002. These results indicate that the 2′-chiral center of DZ2002 plays a critical role for their function. Therefore, quality control to prepare optical (S)-DZ2002 is necessary for further biological studies.Figure optionsDownload as PowerPoint slide