2. Academic Validation
  3. Concise synthesis and biological evaluation of 2-Aroyl-5-amino benzo[b]thiophene derivatives as a novel class of potent antimitotic agents

Concise synthesis and biological evaluation of 2-Aroyl-5-amino benzo[b]thiophene derivatives as a novel class of potent antimitotic agents

  • J Med Chem. 2013 Nov 27;56(22):9296-309. doi: 10.1021/jm4013938.
Romeo Romagnoli 1,  Pier Giovanni Baraldi,  Carlota Lopez-Cara,  Delia Preti,  Mojgan Aghazadeh Tabrizi,  Jan Balzarini,  Marcella Bassetto,  Andrea Brancale,  Xian-Hua Fu,  Yang Gao,  Jun Li,  Su-Zhan Zhang,  Ernest Hamel,  Roberta Bortolozzi,  Giuseppe Basso,  Giampietro Viola
Affiliations

Affiliation

  • 1 Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara , 44121 Ferrara, Italy.
PMID: 24164557 DOI: 10.1021/jm4013938
Abstract

The biological importance of microtubules make them an interesting target for the synthesis of antitumor agents. The 2-(3',4',5'-trimethoxybenzoyl)-5-aminobenzo[b]thiophene moiety was identified as a novel scaffold for the preparation of potent inhibitors of microtubule polymerization acting through the colchicine site of tubulin. The position of the methoxy group on the benzo[b]thiophene was important for maximal antiproliferative activity. Structure-activity relationship analysis established that the best activities were obtained with amino and methoxy groups placed at the C-5 and C-7 positions, respectively. Compounds 3c-e showed more potent inhibition of tubulin polymerization than combretastatin A-4 and strong binding to the colchicine site. These compounds also demonstrated substantial antiproliferative activity, with IC50 values ranging from 2.6 to 18 nM in a variety of Cancer cell lines. Importantly, compound 3c (50 mg/kg), significantly inhibited the growth of the human osteosarcoma MNNG/HOS xenograft in nude mice.

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