New antiplasmodial piperazine alkaloid derivatives from Rauvolfia mannii Stapf. (Apocynaceae)

The stem bark extract of Rauvolfia mannii (Apocynaceae) was submitted to chemical and antiparasitic investigations. Chemical analyses resulted in the isolation of two new furyl-piperazine alkaloid derivatives namely 2-(2 ''-hydroxymethylhexyloxy)furan-5 '-yl)-6-(piperazin-7-yl)piperazine (1) and 2-(2 ''-methylhexyloxy)furan-5 ' yl)-6-(piperazin-7-yl)piperazine (2), along with six known compounds. The structures (including the relative stereochemistry) of these secondary metabolites were determined based on spectroscopic data, chemical correlations and comparison with the literature data. 1 and 2 display at least one piperazine ring, hence induce Rauvolfia alkaloids bearing rare skeletons. They are in fact, reported for the first time from the Apocynaceae family. Additionally, two of the isolates, arjunolic acid (5) and echitamine (7) showed moderate antiplasmodial activity against the chloroquine resistant (CQR) Plasmodium falciparum Dd2 with IC50 values of 22.5 and 16.3 mu g/ mL respectively.