Antitrypanosomal activity of new semi-synthetic bergenin derivatives.

ABSTRACT

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.