New ferrocenic pyrrolo[1,2-a]quinoxaline derivatives: Synthesis, and in vitro antimalarial activity – Part II

• DOI: 10.1016/j.ejmech.2011.03.014
• Publication Date: 2011-03-16T08:20:17Z
• Authors: Jean Guillon; Elisabeth Mouray; Stéphane Moreau; Catherine Mullié; Isabelle Forfar; Vanessa Desplat; Solene Belisle-Fabre; Noël Pinaud; François Ravanello; Augustin Le-Naour; Jean-Michel Léger; Grace Gosmann; Christian Jarry; Gérard Déléris; Pascal Sonnet; Philippe Grellier
• Keywords: Models, Molecular; Dose-Response Relationship, Drug; Molecular Structure; Metallocenes; [SDV]Life Sciences [q-bio]; Plasmodium falciparum; Drug Evaluation, Preclinical; Stereoisomerism; Crystallography, X-Ray; 01 natural sciences; Cell Line; 3. Good health; 0104 chemical sciences; Antimalarials; Structure-Activity Relationship; [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology; Parasitic Sensitivity Tests; Quinoxalines; [CHIM]Chemical Sciences; Humans; Pyrroles; Ferrous Compounds; Cell Proliferation

Following our search for antimalarial compounds, novel series of ferrocenyl-substituted pyrrolo[1,2-a]quinoxalines 1-2 were synthesized from ferrocene-carboxaldehyde and tested for their in vitro activity upon the erythrocytic development of Plasmodium falciparum strains with different chloroquine-resistance status. The ferrocenic pyrrolo[1,2-a]quinoxalines 1-2 were prepared in 6 or 9 steps through a Barton-Zard reaction. Promising pharmacological results against FcB1, K1 and F32 strains were obtained with ferrocenyl pyrrolo[1,2-a]quinoxalines 1j-l linked by a bis-(3-aminopropyl)piperazine linker substituted by a nitrobenzyl moiety.