5-Cinnamoyl-6-aminouracil derivatives as novel anticancer agents. Synthesis, biological evaluation, and structure-activity relationships.
A biological evaluation in the series of 5-cinnamoyl-6-aminouracils has been undertaken. These compounds have been found to be in an extended planar conformation fitting well with a possible stacking interaction between the nucleic bases of DNA; thus an eventual anticancer activity by intercalation could be hoped. 1,3-Dimethyl-5-cinnamoyl-6-aminouracil was found to be active when administered ip against ip-implanted P388 leukemia in vivo (percent T/C = 124). Two other compounds, 1,3-dimethyl-5-cinnamoyl-6-[(2-morpholinoethyl)amino]uracil and 1,3-dimethyl-5-cinnamoyl-6-[(2-piperidinoethyl)amino]uracil, bearing a hydrophilic side chain on the 6-amino group, have exhibited cytoxic activity in vitro against L1210 leukemia. Structure-activity relationships have been determined from these results and from studies of biological interactions with DNA.
Bernier
J L
JL
Hénichart
J P
JP
Warin
V
V
Trentesaux
C
C
Jardillier
J C
JC
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002934:Cinnamates / Q000138:chemical synthesis* / Q000494:pharmacology; D004247:DNA; D004578:Electron Spin Resonance Spectroscopy; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D008815:Mice, Inbred Strains; D008968:Molecular Conformation; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D000970:Antineoplastic Agents; D002934:Cinnamates; D014498:Uracil; D004247:DNA