Author/Authors :
Romeo Romagnoli، نويسنده , , Pier Giovanni Baraldi، نويسنده , , M. Katherine Jung، نويسنده , , Maria Antonietta Iaconinoto، نويسنده , , Maria Dora Carrion، نويسنده , , Vincent Remusat، نويسنده , , Delia Preti، نويسنده , , Mojgan Aghazadeh Tabrizi، نويسنده , , Fruttarolo Francesca، نويسنده , , Erik De Clercq، نويسنده , , Jan Balzarini، نويسنده , , Ernest Hamel، نويسنده ,
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.
