Synthesis and biological evaluation of 2- and 3-aminobenzo[b]thiophene derivatives as antimitotic agents and inhibitors of tubulin polymerization.
Two new series of inhibitors of tubulin polymerization based on the 2-amino-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene molecular skeleton and its 3-amino positional isomer were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. Although many more 3-amino derivatives have been synthesized so far, the most promising compound in this series was 2-amino-6-methyl-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene, which inhibits cancer cell growth at subnanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site.
Romagnoli
Romeo
R
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, 44100 Ferrara, Italy.
Baraldi
Pier Giovanni
PG
Carrion
Maria Dora
MD
Lopez Cara
Carlota
C
Preti
Delia
D
Fruttarolo
Francesca
F
Pavani
Maria Giovanna
MG
Tabrizi
Mojgan Aghazadeh
MA
Tolomeo
Manlio
M
Grimaudo
Stefania
S
Di Cristina
Antonella
A
Balzarini
Jan
J
Hadfield
John A
JA
Brancale
Andrea
A
Hamel
Ernest
E
D000818:Animals; D050256:Antimitotic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D011485:Protein Binding; D011869:Radioligand Assay; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
C520651:2-amino-6-methyl-3-(3,4,5-trimethoxybenzoyl)benzo(b)thiophene; D050256:Antimitotic Agents; D013876:Thiophenes; D014404:Tubulin; D050257:Tubulin Modulators; D003078:Colchicine