NF- κB regulation by bisbenzylisoquinoline alkaloids in human T cells: a structure–activity relationship study

AbstractSuppressive potencies of tetrandrine, isotetrandrine, fangchinoline, berbamine, dauricine, cepharanthine, and armepavine on expression and activation of NF- κB in MOLT-4 cells, MOLT-4/DNR cells, peripheral blood mononuclear cells (PBMCs) of healthy subjects and PBMCs of dialysis patients were compared. In MOLT-4 cells, the suppressive potencies evaluated by the IC50 values were isotetrandrine  >  cepharanthine >  tetrandrine >  dauricine >  fangchinoline >  berbamine or armepavine. In MOLT-4/DNR cells, the order was isotetrandrine >  tetrandrine >  cepharanthine >  fangchinoline >  dauricine >  berbamine or armepavine. In PBMCs of healthy subjects, the order was isotetrandrine >  dauricine >  fangchinoline >  tetrandrine >  cepharanthine >  berbamine or armepavine. In PBMCs of dialysis patients, the order was isotetrandrine >  fangchinoline >  tetrandrine >  cepharanthine >  dauricine >  berbamine or armepavine. Among them, isotetrandrine showed the strongest inhibitory effects on the expression of NF-κB and p-NF-κB in these cells. Accordingly, both 7- and 12-substitutions are suggested to influence the suppressive potency of bisbenzylisoquinoline alkaloids, though 7-substituti on is likely to have less contribution. Bisbenzylisoquinoline alkaloid seems to be more suitable than monobenzylisoquinoline alkaloid to serve as a lead...

Source: Medicinal Chemistry Research - October 7, 2020 Category: Chemistry Source Type: research