The first examples of ilexgenin A hybrids as a new class of multi-potent, anti-platelet agents

Seventeen novel ilexgenin A hybrids (IA-aspirin) and (IA-NO), as donor hybrids (IA-NO will release NO in vivo and function as NO donor), were designed and synthesized in order to develop new multi-targeting agents for the treatment of platelet disorders. Their in vitro activities against ADP, AA and thrombin were evaluated. As a result, IA hybrids achieved substantial increases in the three tested pathways compared with IA. Encouragingly, the most potent hybrid compounds 6d and 14d displayed about 8-fold higher potency than aspirin, and 3-fold higher potency than the simultaneous administration of aspirin and IA in inhibiting ADP-induced aggregation with IC50 values of 0.15 mmol/L and 0.14 mmol/L, respectively. The results suggest these IA hybrids are good candidates for multi-target therapies, and especially, may be considered as promising ADP agonists.

Ilexgenin A (IA) hybrids achieved substantial increases in three tested pathways compared with IA (1). Encouragingly, the most potent compounds 6d and 14d displayed higher potency than aspirin in inhibiting ADP-induced aggregation with IC50 values of 0.15 mmol/L and 0.14 mmol/L, respectively.Figure optionsDownload as PowerPoint slide