Abstract
Carbonic anhydrases (CAs) are one of the promising targets for the development of anticancer agents. CA isoforms are implicated in various physiological processes and are expressed in both normal and cancerous cells. Thus, non-isoform selective inhibitors are associated with several side effects. Consequently, designing selective inhibitors towards cancer-related
CA IX/XII rather than the ubiquitous cytosolic isozymes
CA I and II is the main research objective in the field. Herein, a new series of 3-(6-methylpyridin-2-yl)coumarin derivatives
and
was designed and synthesised. The CA inhibition activities for the synthesised coumarins were analysed on isoforms
CA I, II, IX, and XII. Interestingly, both cancer-linked isoforms
CA IX/XII were inhibited by the prepared coumarins with inhibition constants ranging from sub- to low-micromolar range, whereas
CA I and II isoforms haven't been inhibited up to 100 µM. Furthermore, the target coumarins were assessed for their antitumor activity on NCI-59 human cancer types.