Among the chemotypes studied for selective inhibition of tumour-associated carbonic anhydrases (CAs),
SLC-0111
, a ureido-bearing benzenesulfonamide CA IX inhibitor, displayed promising antiproliferative effects in cancer cells
in vitro
and
in vivo
, being in Phase Ib/II clinical development. To explore the structural characteristics required for better discrimination of less conserved regions of the enzyme, we investigate the incorporation of the urea linker into an imidazolidin-2-one cycle, a modification already explored previously for obtaining CA inhibitors. This new library of compounds inhibited potently four different hCAs in the nanomolar range with a different isoform selectivity profile compared to the lead
SLC-0111
. Several representative CA IX inhibitors were tested for their efficacy to inhibit the proliferation of glioblastoma, pancreatic, and breast cancer cells expressing CA IX, in hypoxic conditions. Unlike previous literature data on
SLC-149
, a structurally related sulphonamide to compounds investigated here, our data reveal that these derivatives possess promising anti-proliferative effects, comparable to those of
SLC-0111
.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.