Abstract
Different 2,4-thiazolidinedione-tethered coumarins
,
and
were synthesised and evaluated for their inhibitory action against the cancer-associated
CAs IX and XII, as well as the physiologically dominant
CAs I and II to explore their selectivity. Un-substituted phenyl-bearing coumarins
,
, and 2-thienyl/furyl-bearing coumarins
exhibited the best
CA IX (K
s between 0.48 and 0.93 µM) and
CA XII (K
s between 0.44 and 1.1 µM) inhibitory actions. Interestingly, none of the coumarins had any inhibitory effect on the off-target
CA I and II isoforms. The sub-micromolar compounds from the biochemical assay, coumarins
,
and
, were assessed in an
antiproliferative assay, and then the most potent antiproliferative agent
was tested to explore its impact on the cell cycle phases and apoptosis in MCF-7 breast cancer cells to provide more insights into the anticancer activity of these compounds.