'Click' synthesis of a triazole-based inhibitor of Met functions in cancer cells.
The use of Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition permitted the synthesis of a new compound that is able to inhibit the HGF-induced scattering of MDCK (epithelial cells) and in vitro tumorigenesis of H1437 (non-small-cell lung cancer) and GTL-16 (human gastric carcinoma). In agreement with biochemical and biological results, docking studies within the ATP binding site of Met suggested for the new synthesized compound a binding mode similar to that of the active compound Triflorcas previously reported.
Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano, Via Venezian 21, 20133 Milano, Italy.
Francesco
F
Colombo
Cristina
C
Tintori
Alessandro
A
Furlan
Stella
S
Borrelli
Michael S
MS
Christodoulou
Rosanna
R
Dono
Flavio
F
Maina
Maurizio
M
Botta
Mercedes
M
Amat
Joan
J
Bosch
Daniele
D
Passarella
D045744:Cell Line, Tumor; D057930:Click Chemistry; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D047428:Protein Kinase Inhibitors; D014230:Triazoles; D019859:Proto-Oncogene Proteins c-met