Synthesis and preliminary biological evaluation of new anti-tubulin agents containing different benzoheterocycles.
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.
Romagnoli
Romeo
R
Dipartimento di Scienze Farmaceutiche, Universitá di Ferrara, Via Fossato di Mortara 17/19, 44100 Ferrara, Italy. rmr@unife.it
Baraldi
Pier Giovanni
PG
Jung
M Katherine
MK
Iaconinoto
Maria Antonietta
MA
Carrion
Maria Dora
MD
Remusat
Vincent
V
Preti
Delia
D
Tabrizi
Mojgan Aghazadeh
MA
Francesca
Fruttarolo
F
De Clercq
Erik
E
Balzarini
Jan
J
Hamel
Ernest
E
D000818:Animals; D001554:Benzene / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003500:Cyclization; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism*
D014404:Tubulin; D001554:Benzene