2. Academic Validation
  3. Synthesis and preliminary biological evaluation of new anti-tubulin agents containing different benzoheterocycles

Synthesis and preliminary biological evaluation of new anti-tubulin agents containing different benzoheterocycles

  • Bioorg Med Chem Lett. 2005 Sep 15;15(18):4048-52. doi: 10.1016/j.bmcl.2005.06.022.
Romeo Romagnoli 1,  Pier Giovanni Baraldi,  M Katherine Jung,  Maria Antonietta Iaconinoto,  Maria Dora Carrion,  Vincent Remusat,  Delia Preti,  Mojgan Aghazadeh Tabrizi,  Fruttarolo Francesca,  Erik De Clercq,  Jan Balzarini,  Ernest Hamel
Affiliations

Affiliation

  • 1 Dipartimento di Scienze Farmaceutiche, Universitá di Ferrara, Via Fossato di Mortara 17/19, 44100 Ferrara, Italy. [email protected]
PMID: 16005627 DOI: 10.1016/j.bmcl.2005.06.022
Abstract

A new series of compounds, in which the 2-amino-4-methoxyphenyl ring of phenstatin analogue 5 was replaced with 2- or 3-amino-benzoheterocycles, was synthesized and evaluated for antiproliferative activity and inhibition of colchicine binding. The lack of activity of 3',4'-dimethoxy- and 4'-methoxy-benzoyl derivatives (8 and 9, respectively) indicates that the 3',4',5'-trimethoxybenzoyl moiety is critical for the activity. Two compounds, 7 and 11, displayed potent antiproliferative activity, with IC50 values ranging from 25 to 100 nM against a variety of Cancer cell lines. Derivative 11 was more active than CA-4 as an inhibitor of tubulin polymerization. The results demonstrated that the antiproliferative activity was correlated with inhibition of tubulin polymerization.

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