Carbonic anhydrase inhibitors. Part 35. Synthesis of Schiff bases derived from sulfanilamide and aromatic aldehydes: the first inhibitors with equally high affinity towards cytosolic and membrane-bound isozymes

Carbonic anhydrase inhibitors

“…[73][74][75][76] Such compounds also appreciably inhibited CA II, and to a smaller extent CA I (Table III). [73][74][75][76] G. Isozyme III Although the structure of this isozyme is relatively similar to that of hCA II, CA III has a CO 2 hydration activity of about 0.3% that of hCA II, as it does not possess a His residue in position 64, but a Lys residue, which is much less effective as a proton shuttle. 77 Furthermore, position 198 in CA III is occupied by a Phe, possessing a very bulky side chain, whereas the water bound to Zn(II) has a pK a around 5.5.…”

“…72 Even so, similarly to CA I, the first compounds with some specificity for CA IV, of type 72-76, were again discovered serendipitously, and they all belong to the same class of Schiff bases of aromatic/heterocyclic sulfonamides. [73][74][75][76] Only Schiff bases of aromatic sulfonamides were investigated in some detail, and it was shown that best CA IV inhibition patterns are connected with the presence of heterocyclic moieties (in the original aldehyde used for the preparation of the Schiff base), or aromatic moieties substituted with electron attracting groups, such as the nitro one. [73][74][75][76] Such compounds also appreciably inhibited CA II, and to a smaller extent CA I (Table III).…”

“…[73][74][75][76] Only Schiff bases of aromatic sulfonamides were investigated in some detail, and it was shown that best CA IV inhibition patterns are connected with the presence of heterocyclic moieties (in the original aldehyde used for the preparation of the Schiff base), or aromatic moieties substituted with electron attracting groups, such as the nitro one. [73][74][75][76] Such compounds also appreciably inhibited CA II, and to a smaller extent CA I (Table III). [73][74][75][76] G. Isozyme III Although the structure of this isozyme is relatively similar to that of hCA II, CA III has a CO 2 hydration activity of about 0.3% that of hCA II, as it does not possess a His residue in position 64, but a Lys residue, which is much less effective as a proton shuttle.…”

Inhibition of carbonic anhydrase isoforms I, II, IX and XII with Schiff’s bases incorporating iminoureido moieties

“…Some of these derivatives were among the first reported sulfonamides showing good selectivity ratios for the inhibition of some human (h) CA isoforms, such as hCA I, II or IV 16,17 . The CA superfamily of enzymes, which act as catalysts for CO 2 hydration to bicarbonate and protons, comprises a large number of genetic families (six, i.e.…”

“…Schiff's bases incorporating sulfonamide functionalities attached to aromatic/heterocyclic moieties of the general formula Ar-CH ¼ N-linker-A-SO 2 NH 2 , have been investigated extensively as carbonic anhydrase (CA, EC 4.2.1.1) [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] inhibitors (CAIs starting with the 1990s when the first such compounds were reported by one of these groups [16][17][18][19][20][21][22][23][24][25][26][27] . Some of these derivatives were among the first reported sulfonamides showing good selectivity ratios for the inhibition of some human (h) CA isoforms, such as hCA I, II or IV 16,17 .…”