Design, synthesis and antiproliferative activity of tripentones: a new series of antitubulin agents.
Structure-activity relationship studies of a new series of tripentones (thieno[2,3-b]pyrrolizin-8-ones), led us to prepare several derivatives with antiproliferative activities. The most promising 3-(3-hydroxy-4-methoxyphenyl)thieno[2,3-b]pyrrolizin-8-one 20 (leukemia L1210, IC(50)=15 nM) was shown to be a potent inhibitor of tubulin polymerization.
Lisowski
V
V
Centre d'Etudes et de Recherche sur le Médicament de Normandie, UFR des Sciences Pharmaceutiques, 1, rue Vaubénard, 14032 Cedex, Caen, France.
Enguehard
C
C
Lancelot
J
J
Caignard
D
D
Lambel
S
S
Leonce
S
S
Pierre
A
A
Atassi
G
G
Renard
P
P
Rault
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007939:Leukemia L1210 / Q000473:pathology; D051379:Mice; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011763:Pyrrolizidine Alkaloids; D050257:Tubulin Modulators