Ureido-substituted sulfamates show potent carbonic anhydrase IX inhibitory and antiproliferative activities against breast cancer cell lines.
A series of 50 sulfamates were obtained by reacting 4-aminophenol with isocyanates followed by sulfamoylation. Most of the new compounds were nanomolar inhibitors of the tumor-associated carbonic anhydrase (CA, EC 4.2.1.1) isoforms IX and XII, whereas they inhibited less cytosolic offtarget isoforms CA I and II. Some of these sulfamates showed significant antiproliferative activity in several breast cancer cell lines, such as SKBR3, MCF10A, ZR75/1, MDA-MB-361 and MCF7, constituting interesting anticancer leads.
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-UM1-UM2, Bâtiment de Recherche Max Mousseron, Ecole Nationale Supérieure de Chimie de Montpellier, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex, France.
Jean-Yves
JY
Winum
Fabrizio
F
Carta
Carol
C
Ward
Peter
P
Mullen
David
D
Harrison
Simon P
SP
Langdon
Alessandro
A
Cecchi
Andrea
A
Scozzafava
Ian
I
Kunkler
Claudiu T
CT
Supuran
D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000737:chemistry* / Q000494:pharmacology
D002257:Carbonic Anhydrase Inhibitors; D013451:Sulfonic Acids; C005741:sulfamic acid; D002256:Carbonic Anhydrases