Alkaloids of Hernandia voyronii: Chloroquine-potentiating activity and structure elucidation of herveline D

Further investigation of Hernandia voyronii led to the isolation of a new pavine-benzyltetrahydroisoquinoline (pavine-BTIQ) dimer, herveline D, together with herveline A, five aporphine alkaloids, two morphinane alkaloids, and their biosynthetic precursor, i.e., the BTIQ (S)-reticuline. Hervelines A-D have a moderate intrinsic in vitro antimalarial activity (IC50 in the range of 1.68-3.28 mu M), but displayed different effects ranging from synergism for herveline B and herveline C to simple additive effect for herveline A, and antagonism for herveline D in a chloroquine (CQ) combination evaluation and this was confirmed in vivo for hervelines A and B. Furthermore, the antiplasmoidal activity of CQ was potentiated in vitro by reticuline and its dimethyl derivative laudanosine (for the latter also in vivo), whereas herveline C moderately potentiated in vitro the antiplasmodial activity of herveline D.