Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Sesto Fiorentino (Florence), Italy.
Department of Biology, Agriculture and Food Sciences, Institute of Biosciences and Bioresources, Napoli, Italy.
J Enzyme Inhib Med Chem. 2023 Dec;38(1):2173748. doi: 10.1080/14756366.2023.2173748.
The γ-carbonic anhydrase (CA, EC 4.2.1.1) from the pathogenic bacterium, (MscCAγ) was recently cloned and purified by our groups. Here we investigated inhibition of this enzyme with (in)organic simple and complex anions, in the search of inhibitors with potential applications. The most effective inhibitors (Ks in the micromolar range) were peroxydisulfate and trithiocarbonate, whereas submillimolar inhibition was observed with -diethyldithiocarbamate and phenylboronic acid (Ks of 0.5-0.9 mM). Thiocyanate, hydrogensulfide, bisulphite, stannate, divanadate, tetraborate, perrhenate, perruthenate, hexafluorophosphate, triflate and iminodisulfonate showed Ks of 1.0-13.7 mM. Cyanate, cyanide, azide, carbonate, nitrate, tellurate, selenocyanide, tetrafluoroborate, sulfamide, sulphamic acid and phenylarsonic acid were weaker inhibitors, with Ks in the range of 25.2-95.5 mM, whereas halides, bicarbonate, nitrite, sulphate, perchlorate and fluorosulfonate did not show inhibitory action up until 100 mM concentrations in the assay system. Finding more effective MscCAγ inhibitors may be helpful to fight drug resistance to antibiotics.
我们小组最近从病原菌中克隆并纯化了γ-碳酸酐酶(CA,EC 4.2.1.1)(MscCAγ)。在这里,我们研究了无机简单和复杂阴离子对该酶的抑制作用,以期寻找具有潜在应用前景的抑制剂。抑制效果最显著的抑制剂(Ks 值在微摩尔范围内)为过二硫酸盐和三硫代碳酸盐,而二乙二硫代氨基甲酸盐和苯硼酸的抑制效果则达到亚毫摩尔水平(Ks 值为 0.5-0.9 mM)。硫氰酸盐、硫化氢、亚硫酸氢盐、锡酸盐、偏钒酸盐、四硼酸盐、高铼酸盐、过钌酸盐、六氟磷酸盐、三氟甲磺酸酯和亚氨基二磺酸酯的 Ks 值为 1.0-13.7 mM。氰酸盐、氰化物、叠氮化物、碳酸盐、硝酸盐、碲酸盐、硒氰化物、四氟硼酸盐、磺胺、氨基磺酸和苯胂酸则是较弱的抑制剂,Ks 值在 25.2-95.5 mM 范围内,而卤化物、碳酸氢盐、亚硝酸盐、硫酸盐、高氯酸盐和氟磺酸盐在实验系统中浓度高达 100 mM 时也没有表现出抑制作用。找到更有效的 MscCAγ 抑制剂可能有助于对抗抗生素耐药性。