2-Arylamino-4-amino-5-aroylthiazoles. "One-pot" synthesis and biological evaluation of a new class of inhibitors of tubulin polymerization.
The essential role of microtubules in mitosis makes them a major target of compounds useful for cancer therapy. In our search for potent antitumor agents, a novel series of 2-anilino-4-amino-5-aroylthiazoles was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. SAR was elucidated with various substitutions on the phenylamino and aroyl moiety at the 2- and 5-positions, respectively, of the 4-aminothiazole skeleton. Tumor cell exposure to several of these compounds led to the arrest of HeLa cells in the G2/M phase of the cell cycle and induction of apoptosis.
Romagnoli
Romeo
R
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Ferrara, Italy. rmr@unife.it
Baraldi
Pier Giovanni
PG
Carrion
Maria Dora
MD
Cruz-Lopez
Olga
O
Cara
Carlota Lopez
CL
Basso
Giuseppe
G
Viola
Giampietro
G
Khedr
Mohammed
M
Balzarini
Jan
J
Mahboobi
Siavosh
S
Sellmer
Andreas
A
Brancale
Andrea
A
Hamel
Ernest
E
D002460:Cell Line; D004583:Electrons; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D055503:Protein Multimerization / Q000187:drug effects*; D020836:Protein Structure, Quaternary; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*
D013844:Thiazoles; D014404:Tubulin