Anti-leishmanial and structure-activity relationship of ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives.
A series of ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives were synthesized and tested for in vitro leishmanicidal activity against amastigotes of Leishmania amazonensis in axenical cultures and murine infected macrophages. Structure-activity relationships demonstrated the importance of a radical methoxy at position R3', R4' and R5'. (2E)-3-(3,4,5-trimethoxy-phenyl)-1-(3,6,7-trimethyl-1,4-dioxy-quinoxalin-2-yl)-propenone was the most active. Cytotoxicity on macrophages revealed that this product was almost six times more active than toxic.
Burguete
Asunción
A
Unidad de Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiología Aplicada, University of Navarra, Campus Universitario, Pamplona, Spain.
Estevez
Yannick
Y
Castillo
Denis
D
González
Germán
G
Villar
Raquel
R
Solano
Beatriz
B
Vicente
Esther
E
Silanes
Silvia Pérez
SP
Aldana
Ignacio
I
Monge
Antonio
A
Sauvain
Michel
M
Deharo
Eric
E
D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D003497:Cyclic N-Oxides / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D007894:Leishmania mexicana / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D021261:Parasitic Sensitivity Tests; D011810:Quinoxalines / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship
D000981:Antiprotozoal Agents; D003497:Cyclic N-Oxides; D011810:Quinoxalines