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Synthesis and Antimalarial Activity of New Enantiopure Aminoalcoholpyrrolo[ 1,2-a]quinoxalines

Abstract : 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 antimalarial activity. 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.
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Soumis le : jeudi 17 mars 2022 - 14:31:01
Dernière modification le : samedi 6 août 2022 - 03:51:14

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Alexia Jonet, Jean Guillon, Catherine Mullie, Anita Cohen, Guillaume Bentzinger, et al.. Synthesis and Antimalarial Activity of New Enantiopure Aminoalcoholpyrrolo[ 1,2-a]quinoxalines. Medicinal Chemistry, Bentham Science Publishers, 2018, 14 (3), pp.293-303. ⟨10.2174/1573406413666170726123938⟩. ⟨hal-03611966⟩

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