The physiologically important and off-target cytosolic isoform hCA I was weakly inhibited by most of the newly synthesized sulfonamides while the glaucoma associated isoform hCA II was moderately inhibited with K<sub>I</sub>s spanning in low nanomolar range (K<sub>I</sub> = 8.0 nM-0.903 μM).
Most of these compounds exhibited excellent activity against all these isoforms. hCA I was inhibited with <i>K<sub>i</sub></i>s in the range of 50.8-966.8 nM, while the glaucoma associated hCA II was inhibited with <i>K<sub>i</sub></i>s in the range of 6.5-760.0 nM.
These compounds were tested for the inhibition of four human (h) isoforms, hCA I, II, IX, and XII, involved in pathologies such as glaucoma (CA II and XII) or cancer (CA IX/XII).
The ureido benzenesulfonamides incorporating triazinyl moieties were investigated as inhibitors of four selected physiologically relevant human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, namely, hCA I, II, IX, and XII which are involved in various diseases such as glaucoma, epilepsy, obesity and cancer.
The obtained 1,3-diaryltriazene-substituted sulfonamides were investigated as inhibitors of four selected human carbonic anhydrase (CA, EC 4.2.1.1) isoforms (hCA I, hCA II, hCA VII and hCA IX) are involved in various diseases such as glaucoma, epilepsy, retinitis pigmentosa, cancer, obesity, etc.
The cytosolic isoform hCA I was inhibited with K<sub>i</sub>'s ranging between 53.2 nM and 7.616 μM whereas the glaucoma associated cytosolic isoform hCA II was inhibited with K<sub>i</sub>'s in the range 21.8 nM-0.807 μM.
Some of these sulfonamides showed effective inhibitory action (in the nanomolar range) against the cytosolic isoform hCA II and the transmembrane, tumor-associated one hCA IX, making them interesting candidates for preclinical evaluation in glaucoma or various tumors in which the two enzymes are involved. hCA I and IV were on the other hand less inhibited by these sulfonamides, with inhibition constants in the micromolar range.