An overview of novel antimicrobial carbonic anhydrase inhibitors.

IF 4.6 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Expert Opinion on Therapeutic Targets Pub Date : 2023-07-01 Epub Date: 2023-10-30 DOI:10.1080/14728222.2023.2263914
Claudiu T Supuran
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引用次数: 2

Abstract

Introduction: Four different genetic families of the enzyme carbonic anhydrase (CA, EC 4.2.1.1) are present in bacteria, α-, β-, γ- and ι-CAs. They play relevant functions related to CO2, HCO3-/H+ ions homeostasis, being involved in metabolic biosynthetic pathways, pH regulation, and represent virulence and survival factors for bacteria in various niches. Bacterial CAs started to be considered druggable targets in the last decade, as their inhibition impairs survival, growth, and virulence of these pathogens.

Areas covered: Significant advances were registered in the last years for designing effective inhibitors of sulfonamide type for Helicobacter pylori α-CA, Neisseria gonorrhoeae α-CA, vacomycin-resistant enterococci (VRE) α- and γ-CAs, for which the in vivo validation has also been achieved. MIC-s in the range of 0.25-4.0 µg/mL for wild type and drug resistant N. gonorrhoeae strains, and of 0.007-2.0 µg/mL for VRE were observed for some 1,3,4-thiadiazole-2-sulfonamides, and acetazolamide was effective in gut decolonization from VRE.

Expert opinion: Targeting bacterial CAs from other pathogens, among which Vibrio cholerae, Mycobacterium tuberculosis, Brucella suis, Salmonella enterica serovar Typhimurium, Legionella pneumophila, Porphyromonas gingivalis, Clostridium perfringens, Streptococcus mutans, Burkholderia pseudomallei, Francisella tularensis, Escherichia coli, Mammaliicoccus (Staphylococcus) sciuri, Pseudomonas aeruginosa, may lead to novel antibacterials devoid of drug resistance problems.

新型抗微生物碳酸酐酶抑制剂综述。
引言:碳酸酐酶(CA,EC 4.2.1.1)在细菌中存在四个不同的遗传家族,即α-、β-、γ-和ι-CA。它们发挥与CO2、HCO3-/H+离子稳态相关的功能,参与代谢生物合成途径、pH调节,并代表不同生态位细菌的毒力和生存因素。在过去的十年里,细菌CA开始被认为是可药用的靶点,因为它们的抑制作用会损害这些病原体的生存、生长和毒力。所涵盖的领域:在过去几年中,在设计有效的磺酰胺类抑制剂治疗幽门螺杆菌α-CA、淋球菌α-CA和耐真空霉素肠球菌(VRE)α-和γ-CA方面取得了重大进展,这些抑制剂也已获得体内验证。MIC-s在0.25-4.0范围内 野生型和耐药性淋球菌菌株为µg/mL,0.007-2.0 一些1,3,4-噻二唑-2-磺酰胺的VRE为µg/mL,乙酰唑胺对VRE的肠道去殖民化有效。专家意见:靶向其他病原体的细菌CA,其中包括霍乱弧菌、结核分枝杆菌、猪布鲁氏菌、伤寒沙门氏菌血清型、嗜肺军团菌、牙龈卟啉单胞菌、产气荚膜梭菌,变形链球菌、假踝伯克霍尔德氏菌、兔弗朗西斯氏菌、大肠杆菌、葡萄球菌、铜绿假单胞菌可能会产生没有耐药性问题的新型抗菌药物。
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来源期刊
CiteScore
8.90
自引率
1.70%
发文量
58
审稿时长
3 months
期刊介绍: The journal evaluates molecules, signalling pathways, receptors and other therapeutic targets and their potential as candidates for drug development. Articles in this journal focus on the molecular level and early preclinical studies. Articles should not include clinical information including specific drugs and clinical trials. The Editors welcome: Reviews covering novel disease targets at the molecular level and information on early preclinical studies and their implications for future drug development. Articles should not include clinical information including specific drugs and clinical trials. Original research papers reporting results of target selection and validation studies and basic mechanism of action studies for investigative and marketed drugs. The audience consists of scientists, managers and decision makers in the pharmaceutical industry, academic researchers working in the field of molecular medicine and others closely involved in R&D.
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