Synthesis of a novel series of cytotoxic bisindole alkaloids.
Original cytotoxic bisindole alkaloids with a 1,2,3,4-tetrahydroquinoline bridge were synthesized by reductive amination with various anilines. The most cytotoxic compounds display a high and dose-dependent cell cycle effect with accumulation in the G1 phase. Influence of substitution of the starting aniline on the reaction and on cytotoxicity of produced dimers was pointed out.
Raoul
M
M
Laboratoire de Pharmacognosie (BIOCIS, UPRES-A 8076 CNRS), Faculté de Pharmacie, Châtenay-Malabry, France.
Schaeffer
C
C
Léonce
S
S
Pierré
A
A
Atassi
G
G
Hocquemiller
R
R
Lewin
G
G
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D002453:Cell Cycle / Q000187:drug effects; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D000814:Aniline Compounds; D000970:Antineoplastic Agents; D007211:Indoles; C023650:aniline