’Abstract

Objectives
 A novel compound 4,4’-diphenylmethane-bis(methyl) carbamate(CM1) was shown to possess preventive activity on AGEs-induced human umbil-ical vein endothelial cells (HUVECs) damage via binding to RAGE. However, theunderlying structural basis of CM1 on binding to RAGE was not fully under-stood.
Methods
 In the present study, CM1 analogues were designed and synthesized tocompare the activity differences on inhibiting AGEs-induced in?ammatoryresponse including TGF-b1, RAGE protein expression in HUVECs, and macro-phages migration and adhesion to HUVECs. In addition, the cell viability andanti-apoptosis activities of CM1 analogues were also examined.
Key ?ndings
 These results indicated that CM1 had higher activities on prevent-ing AGEs-induced HUVECs damage (in?ammation, cell viability and apoptosis)than other analogues. The bioaf?nity assay was conducted by CMC and demon-strated that the IC50and dissociation equilibrium constants (Kd) of CM1 werelower whereas the Bmax was higher than other analogues. The incubation ofRAGE protein with CM1 analogues by equilibrium dialysis method showed CM1had a stronger binding rate than other CM1 analogues.
Conclusion
 Our ?ndings suggested that the C-terminal tails (methoxycarbonylgroups) of CM1 were the active groups for binding to RAGE and then led to theattenuation on RAGE-mediated endothelial dysfunction.