a Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche , Università degli Studi di Firenze , Florence , Italy.
b CNR , Istituto di Bioscienze e Biorisorse , Napoli , Italy.
J Enzyme Inhib Med Chem. 2018 Dec;33(1):1194-1198. doi: 10.1080/14756366.2018.1490733.
The inhibition of α-, β-, γ-, and δ-class carbonic anhydrases (CAs, EC 4.2.1.1) from bacteria (Vibrio cholerae and Porphyromonas gingivalis) and diatoms (Thalassiosira weissflogii) with a panel of N'-aryl-N-hydroxy-ureas is reported. The α-/β-CAs from V. cholerae (VchCAα and VchCAβ) were effectively inhibited by some of these derivatives, with Ks in the range of 97.5 nM - 7.26 µM and 52.5 nM - 1.81 µM, respectively, whereas the γ-class enzyme VchCAγ was less sensitive to inhibition (Ks of 4.75 - 8.87 µM). The β-CA from the pathogenic bacterium Porphyromonas gingivalis (PgiCAβ) was not inhibited by these compounds (Ks > 10 µM) whereas the corresponding γ-class enzyme (PgiCAγ) was effectively inhibited (Ks of 59.8 nM - 6.42 µM). The δ-CA from the diatom Thalassiosira weissflogii (TweCAδ) showed effective inhibition with these derivatives (Ks of 33.3 nM - 8.74 µM). As most of these N-hydroxyureas are also ineffective as inhibitors of the human (h) widespread isoforms hCA I and II (Ks > 10 µM), this class of derivatives may lead to the development of CA inhibitors selective for bacterial/diatom enzymes over their human counterparts and thus to anti-infectives or agents with environmental applications.
报告了一组 N'-芳基-N-羟基脲对来自细菌（霍乱弧菌和牙龈卟啉单胞菌）和硅藻（威氏海链藻）的α-、β-、γ-和δ-碳酸酐酶（CA，EC 4.2.1.1）的抑制作用。这些衍生物有效地抑制了霍乱弧菌（VchCAα 和 VchCAβ）的α-/β-CA，Ks 值分别在 97.5 nM - 7.26 μM 和 52.5 nM - 1.81 μM 范围内，而γ-类酶 VchCAγ 对抑制作用的敏感性较低（Ks 为 4.75 - 8.87 μM）。来自致病菌牙龈卟啉单胞菌的β-CA（PgiCAβ）不受这些化合物的抑制（Ks > 10 μM），而相应的γ-类酶（PgiCAγ）则被有效抑制（Ks 值为 59.8 nM - 6.42 μM）。硅藻威氏海链藻（TweCAδ）的δ-CA 也被这些衍生物有效抑制（Ks 值为 33.3 nM - 8.74 μM）。由于这些 N-羟基脲类化合物对人（h）广泛存在的同工酶 hCA I 和 II 的抑制作用也不明显（Ks > 10 μM），因此，这类衍生物可能会导致开发出对细菌/硅藻酶具有选择性的 CA 抑制剂，而对其人类同工酶则没有选择性，从而开发出抗感染药物或具有环境应用的药物。
