Structure-activity relationships of indole compounds derived from combretastatin A4: synthesis and biological screening of 5-phenylpyrrolo[3,4-a]carbazole-1,3-diones as potential antivascular agents. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue European Journal of Medicinal Chemistry Année : 2010

Structure-activity relationships of indole compounds derived from combretastatin A4: synthesis and biological screening of 5-phenylpyrrolo[3,4-a]carbazole-1,3-diones as potential antivascular agents.

Nancy Ty
Grégory Dupeyre
Guy G Chabot
  • Fonction : Auteur
Johanne Seguin
Lionel Quentin
  • Fonction : Auteur
François Tillequin
  • Fonction : Auteur
Daniel Scherman
  • Fonction : Auteur
Sylvie Michel
  • Fonction : Auteur
Xavier Cachet
  • Fonction : Auteur

Résumé

A series of 5-(3',4',5'-trimethoxyphenyl)pyrrolo[3,4-a]carbazole-1,3(2H,10H)-diones was designed as cis-restricted analogues of 3-aroylindoles, arylthioindoles and 3-benzylidoneindolin-2-ones derived from combretastatin A4 (CA-4). Starting from various indoles, compounds were synthesized by means of a convenient two-step procedure involving a one-pot multicomponent reaction as key step. Intermediate tetrahydro[3,4-a]carbazoles and their corresponding carbazoles were submitted to biological screening tests involved in antivascular action, including the cytotoxicity against murine B16 melanoma cells, the rounding up of endothelial cells (EA.hy 926) and the inhibition of tubulin polymerization. Of the 31 compounds screened, those bearing a methoxy group at the 8-position endowed significant biological activities. A carbazole compound 30 was identified as a promising candidate for further development of novel vascular targeting agents.

Domaines

Chimie organique

Dates et versions

hal-00530041 , version 1 (27-10-2010)

Identifiants

Citer

Nancy Ty, Grégory Dupeyre, Guy G Chabot, Johanne Seguin, Lionel Quentin, et al.. Structure-activity relationships of indole compounds derived from combretastatin A4: synthesis and biological screening of 5-phenylpyrrolo[3,4-a]carbazole-1,3-diones as potential antivascular agents.. European Journal of Medicinal Chemistry, 2010, 45 (9), pp.3726-39. ⟨10.1016/j.ejmech.2010.05.022⟩. ⟨hal-00530041⟩
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