Design, synthesis and biological evaluation of novel 4-alkapolyenylpyrrolo[1,2-a]quinoxalines as antileishmanial agents - Part III

作者：Ronga Luisa; Del Favero Marco; Cohen Anita; Soum Claire; Le Pape Patrice; Savrimoutou Solene; Pinaud Noel; Mullie Catherine; Daulouede Sylvie; Vincendeau Philippe; Farvacques Natacha; Agnamey Patrice; Pagniez Fabrice; Hatter Sebastien; Azas Nadine; Sonnet Pascal; Guillon Jean^*

来源：European Journal of Medicinal Chemistry, 2014, 81: 378-393.

DOI：10.1016/j.ejmech.2014.05.037

• Pyrrolo[1,2-a]quinoxaline
• Antileishmanial activity
• Antitrypanosomal activity
• Antimalarial activity
• Synthesis
• Suzuki reaction

A series of new 4-alkapolyenylpyrrolo[1,2-a]quinoxaline derivatives, original and structural analogues of alkaloid chimanine B and of previously described 4-alkenylpyrrolo[1,2-a]quinoxalines, was synthesized in good yields using efficient palladium-catalyzed Suzuki-Miyaura cross-coupling reactions. These new compounds were tested for in vitro antiparasitic activity upon three Leishmania spp. strains. Biological results showed activity against the promastigote forms of L major, L mexicana and L donovani with IC50 ranging from 1.2 to 14.7 mu M. In attempting to investigate if our pyrrolo[1,2-a]quinoxaline derivatives are broad-spectrum antiprotozoal compounds activities toward one Trypanosoma brucei brucei strain and the W2 and 3D7 Plasmodium falciparum strains were also investigated. In parallel, the in vitro cytotoxicity of these molecules was assessed on the murine J774 and human HepG2 cell lines. Structure activity relationships of these new synthetic compounds are here discussed.

• 出版日期2014-6-23