Synthesis and biological evaluation of 1-methyl-2-(3',4',5'-trimethoxybenzoyl)-3-aminoindoles as a new class of antimitotic agents and tubulin inhibitors.
The 2-(3,4,5-trimethoxybenzoyl)-2-aminoindole nucleus was used as the fundamental structure for the synthesis of compounds modified with respect to positions C-4 to C-7 with different moieties (chloro, methyl, or methoxy). Additional structural variations concerned the indole nitrogen, which was alkylated with small alkyl groups such as methyl or ethyl. We have identified 1-methyl-2-(3,4,5-trimethoxybenzoyl)-3-amino-7-methoxyindole as a new highly potent antiproliferative agent that targets tubulin at the colchicine binding site and leads to apoptotic cell death.
Romagnoli
Romeo
R
Dipartimento di Scienze Farmaceutiche, Universita di Ferrarra, Italy. rmr@unife.it
Baraldi
Pier Giovanni
PG
Sarkar
Taradas
T
Carrion
Maria Dora
MD
Cara
Carlota Lopez
CL
Cruz-Lopez
Olga
O
Preti
Delia
D
Tabrizi
Mojgan Aghazadeh
MA
Tolomeo
Manlio
M
Grimaudo
Stefania
S
Di Cristina
Antonella
A
Zonta
Nicola
N
Balzarini
Jan
J
Brancale
Andrea
A
Hsieh
Hsing-Pang
HP
Hamel
Ernest
E
D000818:Animals; D050256:Antimitotic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D001704:Biopolymers; D045744:Cell Line, Tumor; D003078:Colchicine / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008958:Models, Molecular; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
C529300:1-methyl-2-(3',4',5'-trimethoxybenozyl)-3-amino-7-methoxyindole; D050256:Antimitotic Agents; D001704:Biopolymers; D007211:Indoles; D014404:Tubulin; D050257:Tubulin Modulators; D003078:Colchicine