Background: We prepared a novel series of enantiopure mefloquine analogues with pyrrolo[
1,2-a]quinoxaline core in order to fight Plasmodium falciparum resistant strain.
Objectives: To observe the influence of pyrrolo[1,2-a]quinoxaline core versus quinoline core on the
Method: Four enantiopure aminoalcoholpyrrolo[1,2-a]quinoxalines 2 were synthetized via Sharpless
asymmetric dihydroxylation reaction in eight steps. Their antimalarial activity was evaluated on two
Plasmodium falciparum strains 3D7 and W2 with a SYBR Green I fluorescence-based method and
their cytotoxicity was measured on four cell lines HepG2, THP-1, CHO and HFF.
Results: IC50 values of the four compounds 2 were close to the micromolar against the two P. falciparum
strains. They were more active against P. falciparum strain W2 vs. P. falciparum strain 3D7. (R)-
enantiomers were always more active than their (S)-counterpart whatever the strain. Selectivity indexes
of compounds 2 were lower than 100.
Conclusion: A novel series of enantiopure aminoalcohols with pyrrolo[1,2-a]quinoxaline core were
synthesized in eight steps. They displayed IC50 values close to the micromolar against two P. falciparum
strains 3D7 and W2. Although, In this series, 2,8-bistrifluoromethylquinoline was a best core than
pyrrolo[1,2-a]quinoxaline for an optimal antimalarial activity, the pyrroloquinoxaline 2b showed an
interesting antimalarial activity.