Synthesis of new 4-(E)-alkenylpyrrolo[1,2-a]quinoxalines as antileishmanial agents by Suzuki-Miyaura cross-coupling reactions.
A series of new 4-(E)-alkenylpyrrolo[1,2-a]quinoxaline derivatives, structural analogues of alkaloid chimanine B, was synthesized in good yields using efficient palladium(0)-catalyzed Suzuki-Miyaura cross-coupling reactions. These new compounds were tested for in vitro antiparasitic activity upon Leishmania amazonensis and Leishmania infantum strains. Biological results showed activity against the promastigote forms of L. amazonensis and L. infantum with IC50 ranging from 0.5 to 7 microM. From a Structure-Activity Relationships point of view, these pharmacological results mainly enlightened the importance of the 4-lateral C6, C7 or C8 alpha-unsaturated trans-alkenyl chain of unsubstituted pyrrolo[1,2-a]quinoxaline moiety.
EA 4138-Pharmacochimie, UFR des Sciences Pharmaceutiques, Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France. Jean.Guillon@chimphys.u-bordeaux2.fr
Jean
J
Guillon
Isabelle
I
Forfar
Vanessa
V
Desplat
Solene Belisle
SB
Fabre
Denis
D
Thiolat
Stephane
S
Massip
Helene
H
Carrie
Djavad
D
Mossalayi
Christian
C
Jarry
D000818:Animals; D000977:Antiparasitic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D020128:Inhibitory Concentration 50; D018314:Leishmania infantum / Q000187:drug effects*; D007894:Leishmania mexicana / Q000187:drug effects*; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D018675:Toxicity Tests
D000977:Antiparasitic Agents; D011810:Quinoxalines