Natural product hybrid and its superacid synthesized analogues: Dodoneine and its derivatives show selective inhibition of carbonic anhydrase isoforms I, III, XIII and XIV

Abstract

The natural product dodoneine (a dihydropyranone phenolic compound), extracted from African mistletoe Agelanthus dodoneifolius, has been investigated as inhibitor of several human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms. By using superacid chemistry, analogues of the lactone phenolic hybrid lead compound have been synthesized and tested as CA inhibitors. Small chemical modifications of the basic scaffold revealed strong changes in the selectivity profile against different CA isoforms. These new compounds selectively inhibited isoforms CA I (KIs in the range of 0.13–0.76μM), III (KIs in the range of 5.13–10.80μM), XIII (KIs in the range of 0.34–0.96μM) and XIV (KIs in the range of 2.44–7.24μM), and can be considered as new leads, probably acting as non-zinc-binders, similar to other phenols/lactones investigated earlier.