In this work, different series of benzothiazole-based sulphonamides
8a-c, 10, 12, 16a-b
and carboxylic acids
14a-c
were developed as novel SLC-0111 analogues with the goal of generating potent carbonic anhydrase (CA) inhibitors. The adopted strategy involved replacing the 4-fluorophenyl tail in SLC-0111 with a benzothiazole motif that attached to the ureido linker to produce compounds
8c
and its regioisomers
8a-b
. In addition, the ureido spacer was elongated by methylene or ethylene groups to afford the counterparts
10
and
12
. In turn, the primary sulfamoyl zinc binding group (ZBG) was either substituted or replaced by carboxylic acid functionality in order to provide the secondary sulphonamide-based SLC-0111 analogues
16a-b
, and the carboxylic acid derivatives
14a-c
, respectively. All compounds (
8a-c, 10, 12, 14a-c
and
16a-b
) were tested for their ability to inhibit CA isoforms CA I, II, IX and XII. Additionally, the
in vitro
anticancer properties of the developed CAIs were evaluated.
Different 2,4-thiazolidinedione-tethered coumarins
5a–b
,
10a–n
and
11a–d
were synthesised and evaluated for their inhibitory action against the cancer-associated
h
CAs IX and XII, as well as the physiologically dominant
h
CAs I and II to explore their selectivity. Un-substituted phenyl-bearing coumarins
10a
,
10 h
, and 2-thienyl/furyl-bearing coumarins
11a–c
exhibited the best
h
CA IX (K
I
s between 0.48 and 0.93 µM) and
h
CA XII (K
I
s between 0.44 and 1.1 µM) inhibitory actions. Interestingly, none of the coumarins had any inhibitory effect on the off-target
h
CA I and II isoforms. The sub-micromolar compounds from the biochemical assay, coumarins
10a
,
10 h
and
11a–c
, were assessed in an
in vitro
antiproliferative assay, and then the most potent antiproliferative agent
11a
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.
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