Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
Bioorg Med Chem Lett. 2011 Apr 15;21(8):2521-6. doi: 10.1016/j.bmcl.2011.02.057. Epub 2011 Feb 17.
The inhibition of the β-carbonic anhydrases (CAs, EC 4.2.1.1) from the pathogenic fungi Cryptococcus neoformans (Can2) and Candida albicans (Nce103) with a series of 25 branched aliphatic and aromatic carboxylates has been investigated. Human isoforms hCA I and II were also included in the study for comparison. Aliphatic carboxylates were generally millimolar hCA I and II inhibitors and low micromolar/submicromolar β-CA inhibitors. Aromatic carboxylates were micromolar inhibitors of the four enzymes but some of them showed low nanomolar activity against the fungal pathogenic enzymes. 4-Hydroxy- and 4-methoxy-benzoate inhibited Can2 with K(I)s of 9.5-9.9 nM. The methyl esters, hydroxamates, hydrazides and carboxamides of some of these derivatives were also effective inhibitors of the α- and β-CAs investigated here.
研究了一系列 25 种支链脂肪族和芳香族羧酸酯对致病性真菌新生隐球菌（Can2）和白色念珠菌（Nce103）的β-碳酸酐酶（CA，EC 4.2.1.1）的抑制作用。同时还研究了人同工型 hCA I 和 II，以便进行比较。脂肪族羧酸酯通常是毫摩尔级 hCA I 和 II 的抑制剂，也是低微摩尔/亚微摩尔β-CA 的抑制剂。芳香族羧酸酯是四种酶的微摩尔抑制剂，但其中一些对真菌致病酶表现出低纳摩尔活性。4-羟基-和 4-甲氧基苯甲酸对 Can2 的抑制常数（K(i)）为 9.5-9.9 nM。这些衍生物的甲酯、羟肟酸、酰肼和酰胺也是这里研究的α-和β-CA 的有效抑制剂。
