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 morphinan e alkaloids, and their biosynthetic precursor, i.e., the BTIQ (S)-reti culine. Hervelines A-D have a moderate intrinsic in vitro antimalarial activity (IC50 in the range of 1.68-3.28 mu M), but displayed differe nt effects ranging from synergism for herveline B and herveline C to s imple 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 derivat ive laudanosine (for the latter also in vivo), whereas herveline C mod erately potentiated in vitro the antiplasmodial activity of herveline D.