Neurofarba Department, Pharmaceutical and Nutraceutical Section, University of Florence, Sesto Fiorentino, Italy.
Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN, USA.
J Enzyme Inhib Med Chem. 2022 Dec;37(1):666-671. doi: 10.1080/14756366.2022.2038592.
The α-class carbonic anhydrases (CAs, EC 4.2.1.1) from the bacterial pathogens (NgCAα) and (VchCAα) were investigated for their inhibition by a panel of phenols and phenolic acids. Mono-, di- and tri-substituted phenols incorporating additional hydroxyl/hydroxymethyl, amino, acetamido, carboxyl, halogeno and carboxyethenyl moieties were included in the study. The best NgCAα inhibitrs were phenol, 3-aminophenol, 4-hydroxy-benzylalcohol, 3-amino-4-chlorophenol and paracetamol, with K values of 0.6-1.7 µM. The most effective VchCAα inhibitrs were phenol, 3-amino-4-chlorophenol and 4-hydroxy-benzyl-alcohol, with K values of 0.7-1.2 µM. Small changes in the phenol scaffold led to drastic effects on the bacterial CA inhibitory activity. This class of underinvestigated bacterial CA inhibitors may thus lead to effective compounds for fighting drug resistant bacteria.
研究了来自细菌病原体 （NgCAα）和 （VchCAα）的α 类碳酸酐酶（CAs，EC 4.2.1.1）被一组酚类和酚酸抑制的情况。研究中包括了单取代、二取代和三取代酚，它们具有额外的羟基/羟甲基、氨基、乙酰氨基、羧基、卤素和羧基乙烯基部分。对 NgCAα 抑制作用最好的抑制剂是苯酚、3-氨基酚、4-羟基苯甲醇、3-氨基-4-氯苯酚和扑热息痛，其 K 值为 0.6-1.7 μM。对 VchCAα 抑制作用最强的抑制剂是苯酚、3-氨基-4-氯苯酚和 4-羟基苯甲醇，其 K 值为 0.7-1.2 μM。酚类支架的微小变化对细菌 CA 抑制活性有很大影响。因此，这一类研究较少的细菌 CA 抑制剂可能会产生对抗耐药菌的有效化合物。
