Vullo Daniela, Lehneck Ronny, Donald William A, Pöggeler Stefanie, Supuran Claudiu T
Dipartimento di Chimica Ugo Schiff, Università degli Studi di Firenze, 50019 Sesto Fiorentino (Florence), Italy.
Institute of Microbiology and Genetics, Department of Genetics of Eukaryotic Microorganisms, Georg-August-University Göttingen, 37077 Gottingen, Germany.
Metabolites. 2020 Mar 5;10(3):93. doi: 10.3390/metabo10030093.
CAS3 is a newly cloned cytosolic β-class carbonic anhydrase (CA, EC 4.2.1.1) from the filamentous ascomycete . This enzyme has a high catalytic activity for the physiological CO hydration reaction and herein, we report the inhibition profile of CAS3 with anions and small molecules. The most effective CAS3 anions/small molecule inhibitors were diethyl-dithiocarbamate, sulfamide, sulfamate, phenyl boronic and phenyl arsonic acids, with Ks in the range of 0.89 mM-97 µM. Anions such as iodide, the pseudohalides, bicarbonate, carbonate, nitrate, nitrite, hydrogensulfide, stannate, selenate, tellurate, tetraborate, perrhenate, perruthenate, selenocyanide and trithiocarbonate were low millimolar CAS3 inhibitors. The light halides, sulfate, hydrogensulfite, peroxydisulfate, diphosphate, divanadate, perchlorate, tetrafluoroborate, fluorosulfonate and iminodisulfonate did not significantly inhibit this enzyme. These data may be useful for developing antifungals based on CA inhibition, considering the fact that many of the inhibitors reported here may be used as lead molecules and, by incorporating the appropriate organic scaffolds, potent nanomolar inhibitors could be developed.
CAS3是一种新克隆的来自丝状子囊菌的胞质β类碳酸酐酶（CA，EC 4.2.1.1）。该酶对生理性CO水合反应具有高催化活性，在此我们报道了CAS3与阴离子和小分子的抑制谱。最有效的CAS3阴离子/小分子抑制剂是二乙基二硫代氨基甲酸盐、氨磺酰胺、氨基磺酸盐、苯硼酸和苯胂酸，其Ks在0.89 mM至97 μM范围内。碘化物、拟卤化物、碳酸氢盐、碳酸盐、硝酸盐、亚硝酸盐、硫化氢、锡酸盐、硒酸盐、碲酸盐、四硼酸盐、高铼酸盐、高钌酸盐、硒氰化物和三硫代碳酸盐等阴离子是低毫摩尔浓度的CAS3抑制剂。轻卤化物、硫酸盐、亚硫酸氢盐、过二硫酸盐、二磷酸盐、二钒酸盐、高氯酸盐、四氟硼酸盐、氟磺酸盐和亚氨基二磺酸盐对该酶没有显著抑制作用。考虑到这里报道的许多抑制剂可作为先导分子，并且通过引入合适的有机支架可以开发出有效的纳摩尔级抑制剂，这些数据可能有助于基于CA抑制开发抗真菌剂。
