1454891-19-0Relevant academic research and scientific papers
Synthesis and biological evaluation of cyclic imides incorporating benzenesulfonamide moieties as carbonic anhydrase I, II, IV and IX inhibitors
Abdel-Aziz, Alaa A.-M.,Angeli, Andrea,El-Azab, Adel S.,Abu El-Enin, Mohamed A.,Supuran, Claudiu T.
, p. 1666 - 1671 (2017/02/26)
A group of cyclic imides was synthesized by reaction of amino-substituted benzenesulfonamides with a series of acid anhydrides such as succinic, maleic, tetrahydrophthalic, pyrazine-2,3-dicarboxylic acid anhydride, and substituted phthalic anhydrides. The synthesized sulfonamides were evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors against the human (h) isoforms hCA I, II, IV and IX, involved in a variety of diseases among which glaucoma, retinitis pigmentosa, etc. 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.
Carbonic anhydrase inhibitors: Synthesis and inhibition of the human carbonic anhydrase isoforms I, II, VII, IX and XII with benzene sulfonamides incorporating 4,5,6,7-tetrabromophthalimide moiety
Sethi, Kalyan K.,Vullo, Daniella,Verma, Saurabh M.,Tanc, Muhammet,Carta, Fabrizio,Supuran, Claudiu T.
, p. 5973 - 5982 (2013/09/23)
A series of 4,5,6,7-tetrabromo-1,3-dioxoisoindolin-2-yl benzenesulfonamide derivatives (compounds 1-8) was synthesized by reaction of benzene sulfonamide derivatives with 4,5,6,7-tetrabromophthalic anhydride moiety. These new sulfonamides were investigated as inhibitors of the zinc metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) and more specifically against the human (h) cytosolic isoforms hCA I, II and VII and the transmembrane tumor-associated isoform hCA IX and XII. The new compounds were good hCA I inhibitors (Kis in the range of 143 to >10,000 nM), but were moderately effective, as hCA II inhibitors (Kis of 47-190 nM) and poor hCA VII inhibitors (Kis in the range of 54-175 nM) compared to acetazolamide. The tumor-associated hCA IX was effectively inhibited with Kis ranging between 8.5 and 234 nM and hCA XII with inhibition constants in the range of 6.1-197 nM with high selectivity ratio. The structure-activity relationship (SAR) with this series of sulfonamides is straightforward, with the main features leading to good activity for each isoforms being established. The high sequence hCA alignment homology and molecular docking study of compounds was performed to rationalize the SAR reported over here.
