Inhibition of α-, β-, γ-, and δ-carbonic anhydrases from bacteria and diatoms with N′-aryl-N-hydroxy-ureas

Journal of Enzyme Inhibition and Medicinal Chemistry

Clemente Capasso¹  Fatmah A. S. Alasmary²  Zeid AlOthman²  Linah S. Alqahtani²  Sonia Del Prete³  Murat Bozdag³  Claudiu T. Supuran³  Emanuela Berrino³ 

[1] Istituto di Bioscienze e Biorisorse;King Saud University;Università degli Studi di Firenze;

关键词: Carbonic anhydrase;    metalloenzymes;    protozoa;    activators;    Plasmodium falciparum;   

DOI  :  10.1080/14756366.2018.1490733

来源: DOAJ

【 摘 要 】

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 KIs 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 (KIs of 4.75 – 8.87 µM). The β-CA from the pathogenic bacterium Porphyromonas gingivalis (PgiCAβ) was not inhibited by these compounds (KIs > 10 µM) whereas the corresponding γ-class enzyme (PgiCAγ) was effectively inhibited (KIs of 59.8 nM – 6.42 µM). The δ-CA from the diatom Thalassiosira weissflogii (TweCAδ) showed effective inhibition with these derivatives (KIs 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 (KIs > 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.

【 授权许可】

Unknown