Synthesis and biological evaluation of 1-methyl-2-(3',4',5'-trimethoxybenzoyl)-3-aminoindoles as a new class of antimitotic agents and tubulin inhibitors

  • J Med Chem. 2008 Mar 13;51(5):1464-8. doi: 10.1021/jm7011547.
Romeo Romagnoli  1 ,  Pier Giovanni Baraldi ,  Taradas Sarkar ,  Maria Dora Carrion ,  Carlota Lopez Cara ,  Olga Cruz-Lopez ,  Delia Preti ,  Mojgan Aghazadeh Tabrizi ,  Manlio Tolomeo ,  Stefania Grimaudo ,  Antonella Di Cristina ,  Nicola Zonta ,  Jan Balzarini ,  Andrea Brancale ,  Hsing-Pang Hsieh ,  Ernest Hamel
Affiliations
  • 1. Dipartimento di Scienze Farmaceutiche, Universita di Ferrarra, Italy. [email protected]
PMID: 18260616 DOI: 10.1021/jm7011547
Abstract

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.