6-Triazolyl-substituted sulfocoumarins are potent, selective inhibitors of the tumor-associated carbonic anhydrases IX and XII

7-Aryl-triazolyl-substituted sulfocoumarins are potent, selective inhibitors of the tumor-associated carbonic anhydrase IX and XII

“…(i) According to our previous reports [40][41][42][43][44] , isoform hCA I was not or was poorly inhibited by sulfocoumarins 7-14. Compounds 8 and 11 are high micromolar inhibitors, whereas the remaining ones did not significantly inhibit the enzyme below 10 mm inhibitor concentration.…”

“…Many synthetic efforts have been made for the development of specific CAIs: in the last 15 years, in addition to the classical ''tail approach'' [10][11][12][13][14][15][16][17][25][26][27][28] which is mainly applied to classical sulfonamide inhibitors and their isosters, novel CAIs scaffolds have been also identified such as the polyamines 29 , phenols [30][31][32] , dithiocarbamates [33][34][35][36] , xanthates 37 , coumarins, thiocoumarins, 2-thioxocoumarins, coumarine oximes 4,38,39 . Sulfocoumarins are the latest CAI class identified and similarly to the coumarins showed the most selective inhibition profiles against the pathologically valuable CA isoforms 1,9,[40][41][42][43][44] . In analogy to coumarins, the substitution pattern at the sulfocoumarin scaffolds strongly influences the potency and selectivity profile against different hCA isoforms 1, [40][41][42][43][44] .…”

“…Sulfocoumarins are the latest CAI class identified and similarly to the coumarins showed the most selective inhibition profiles against the pathologically valuable CA isoforms 1,9,[40][41][42][43][44] . In analogy to coumarins, the substitution pattern at the sulfocoumarin scaffolds strongly influences the potency and selectivity profile against different hCA isoforms 1, [40][41][42][43][44] . Indeed, in our previous reports [40][41][42][43] , we investigated large series of sulfocoumarins bearing the tetrazolyl, triazolyl or aryl/alkyl moieties at 6 position, which showed low nanomolar hCAIX/ XII inhibitory potencies, without particular effects on the cytosolic hCAI/II.…”

“…In analogy to coumarins, the substitution pattern at the sulfocoumarin scaffolds strongly influences the potency and selectivity profile against different hCA isoforms 1, [40][41][42][43][44] . Indeed, in our previous reports [40][41][42][43] , we investigated large series of sulfocoumarins bearing the tetrazolyl, triazolyl or aryl/alkyl moieties at 6 position, which showed low nanomolar hCAIX/ XII inhibitory potencies, without particular effects on the cytosolic hCAI/II. On the contrary, derivatives bearing small substituents as well as benzyl esters at the 7 position act as low nanomolar hCAII inhibitors 40 .…”

Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications

“…A diverse set of 1,5-triazole products can be found in these reports which cover a wide range of targets and target classes including various enzyme inhibitors, [203][204][205][206][207][208][209][210][211][212][213] kinases, [214][215][216][217] proteases, 110,112 antivirals 218 (see also chapter 5.3) G-protein coupled receptors (GPCRs), 219 ion channels, [220][221][222] heat shock proteins, 95 and tRNA ligands. 223 1,5-Triazole derivatives have shown activity against numerous cancer cell lines, 205,215,[224][225][226][227] and against the parasites Trypanosoma cruzi 70,228 and Plasmodium falciparum.…”