Synthesis and biological evaluation of 1-methyl-2-(3',4',5'-trimethoxybenzoyl)-3-aminoindoles as a new class of antimitotic agents and tubulin inhibitors
Romagnoli, Romeo × Baraldi, Pier Giovanni Sarkar, Taradas Carrion, Maria Dora Cara, Carlota Lopez Cruz-Lopez, Olga Preti, Delia Tabrizi, Mojgan Aghazadeh Tolomeo, Manlio Grimaudo, Stefania Di Cristina, Antonella Zonta, Nicola Balzarini, Jan Brancale, Andrea Hsieh, Hsing-Pang Hamel, Ernest #
Journal of Medicinal Chemistry vol:51 issue:5 pages:1464-1468
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.