A new series of compds. in which the 2-amino-5-chlorophenyl ring of 3,4,5-(MeO)3C6H2COC6H4(NH2)Cl-2,5 was replaced with a 2-amino-5-arylthiophene was synthesized and evaluated for antiproliferative activity and for inhibition of tubulin polymn. and colchicine binding to tubulin. 2-Amino-3-(3,4,5-trimethoxybenzoyl)-5-phenylthiophene and its 4-F (I), 4-Me (II), and 4-MeO derivs. displayed high antiproliferative activities with IC50 values from 2.5 to 6.5 nM against the L1210 and K562 cell lines. I and II were more active than combretastatin A-4 as inhibitors of tubulin polymn. Mol. docking simulations to the colchicine site of tubulin were performed to det. the possible binding mode of I. The results obtained demonstrated that antiproliferative activity correlated well with the inhibition of tubulin polymn. and the lengthening of the G2/M phase of the cell cycle. Moreover, a good correlation was found between these inhibitory effects and the induction of apoptosis in cells treated with the compds.
Synthesis and biological evaluation of 2-amino-3-(3 ',4 ',5 '-trimethoxybenzoyl)-5-aryl thiophenes as a new class of potent antitubulin agents
ROMAGNOLI, Romeo;BARALDI, Pier Giovanni;PAVANI, Maria Giovanna;AGHAZADEH TABRIZI, Mojgan;PRETI, Delia;FRUTTAROLO, Francesca;PICCAGLI, Laura;BORGATTI, Monica;GAMBARI, Roberto
2006
Abstract
A new series of compds. in which the 2-amino-5-chlorophenyl ring of 3,4,5-(MeO)3C6H2COC6H4(NH2)Cl-2,5 was replaced with a 2-amino-5-arylthiophene was synthesized and evaluated for antiproliferative activity and for inhibition of tubulin polymn. and colchicine binding to tubulin. 2-Amino-3-(3,4,5-trimethoxybenzoyl)-5-phenylthiophene and its 4-F (I), 4-Me (II), and 4-MeO derivs. displayed high antiproliferative activities with IC50 values from 2.5 to 6.5 nM against the L1210 and K562 cell lines. I and II were more active than combretastatin A-4 as inhibitors of tubulin polymn. Mol. docking simulations to the colchicine site of tubulin were performed to det. the possible binding mode of I. The results obtained demonstrated that antiproliferative activity correlated well with the inhibition of tubulin polymn. and the lengthening of the G2/M phase of the cell cycle. Moreover, a good correlation was found between these inhibitory effects and the induction of apoptosis in cells treated with the compds.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
