Antitrypanosomal activity of new semi-synthetic bergenin derivatives

Bergenin and 11-O-(4'-O-methyl galloyl)-bergenin, previously isolated from Crassula capitella extract, were used as starting materials for the synthesis of eight derivatives; four derivatives 2a-2d were synthesized from bergenin through the formation of ester derivatives and four alkyl derivatives 4a-4d were synthesized from 11-O-(4'-O-methyl galloyl)-bergenin. The structures of the synthesized analogues were confirmed upon ¹ H and ¹³ C NMR spectroscopic elucidation. Antileishmanial and antitrypanosomal activities of the synthesized derivatives were evaluated, compounds 11-O-(3',5' di-benzyl, 4'-O-methyl galloyl)-8,10-di-O-benzyl-bergenin (4c) and 11-O-(3',5'di-4-chlorobenzyl,4'-O-methyl galloyl)-8,10di-O-4-chlorobenzyl bergenin (4d) showed potent antitrypanosomal activity with IC₅₀ values of 0.52 and 0.5 μM, respectively and IC₉₀  values of 0.66 μM against T. brucei compared with IC₅₀ and IC₉₀ values of 21.7 and 50.3 μM for the positive control difluoromethylornithine.