Carbonic anhydrase inhibitors: Design, synthesis and structural characterization of new heteroaryl-N-carbonylbenzenesulfonamides targeting druggable human carbonic anhydrase isoforms

Thermodynamic, kinetic, and structural parameterization of human carbonic anhydrase interactions toward enhanced inhibitor design

“…The second rings of both compounds have alternate positions in the active site. Heteroaryl-benzenesulfonamides were tested as isoform-specific inhibitors with several CA isoforms and their binding to CA II was analyzed in five crystal structures (Buemi et al ., 2015). Ligands in all five structures coincided well and were bound hydrophobically.…”

Identification of influenza PA-Nter endonuclease inhibitors using pharmacophore- and docking-based virtual screening

“…Using this pharmacophore model, we performed an in silico screening campaign on our CHIME 1.6 library, which consists of a collection of 1300 small molecules developed and synthesized in our laboratory during the last decade. In particular, our compound collection contains a large number of indole derivatives, [26][27][28][29][30][31][32] benzenesulfonamides, [33][34][35] and isoquinolines. 26,[36][37][38][39] As result of this VS, the best hits were the 1-(5,6-dihydroxy-1Hindol-3-yl)-3-[4-[(4-fluorophenyl)methyl]-1-piperidyl]propan-1-one (18), 25 1-(4-benzyl-1-piperidyl)-2-(5,6-dihydroxy-1H-indol-3-yl) ethane-1,2-dione ( 19) 26 and N-[2- (3,4-dihydroxyphenyl)ethyl]-4-sulfamoylbenzamide (20).…”

“…By employing previously reported procedures, we obtained derivatives 19 27 and 20. 34 The enzymatic assay was performed according to a previously published method with minor modifications. 44 Recombinant PA-Nter (0.3 µg) was incubated with the test compounds and 1 μg (16.7 nM) of single-stranded circular DNA plasmid M13mp18 substrate (Bayou Biolabs, Metairie, Louisiana).…”

Seeking new approach for therapeutic treatment of cholera disease via inhibition of bacterial carbonic anhydrases: experimental and theoretical studies for sixteen benzenesulfonamide derivatives

“…Most of these inhibitors represent interesting leads towards the optimisation of new antibiotic agents showing excellent inhibitory efficiency and selectivity for the target CAs over the human (h) offtarget isoform hCA I 10,11 . In the course of our efforts to identify novel selective CAIs, we have synthesised and tested a series of quinolone/isoquinoline-arylsulfonamides showing high affinity toward human CAs [12][13][14][15][16][17][18][19][20][21][22] . Specifically, we have reported the discovery of a set of heteroaryl-N-carbonylbenzenesulfonamides as a class of potent inhibitors of druggable CA isoforms (hCA II, hCA VII, hCA IX, and hCA XIV) 15,17,18,[20][21][22] .…”