Synthesis, molecular modelling and QSAR study of new N- phenylacetamide-2-oxoindole benzensulfonamide conjugates as carbonic anhydrase inhibitors with antiproliferative activity.

In continuation of our previous studies to optimise potent carbonic anhydrase inhibitors, two new series of isatin N- phenylacetamide based sulphonamides were synthesised and screened for their human (h) carbonic anhydrase (EC 4.2.1.1) inhibitory activities against four isoforms h CA I, h CA II, h CA IX and h CA XII. The indole-2,3-dione derivative 2h showed the most effective inhibition profile against h CAI and h CA II (K I = 45.10, 5.87 nM) compared to acetazolamide ( AAZ) as standard inhibitor. Moreover, 2h showed appreciable inhibition activity against the tumour-associated h CA XII, similar to AAZ showing K I of 7.91 and 5.70 nM, respectively. The analogs 3c and 3d showed good cytotoxicity effects, and 3c revealed promising selectivity towards lung cell line A549. Molecular docking was carried out for 2h and 3c to predict their binding conformations and affinities towards the h CA I, II, IX and XII isoforms.