Mohammad Sadegh Gheibzadeh, Clemente Capasso, Claudiu T Supuran, Reza Zolfaghari Emameh
{"title":"针对霍乱弧菌酶的抗菌碳酸酐酶抑制剂。","authors":"Mohammad Sadegh Gheibzadeh, Clemente Capasso, Claudiu T Supuran, Reza Zolfaghari Emameh","doi":"10.1080/14728222.2024.2369622","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Cholera is a bacterial diarrheal disease caused by pathogen bacteria Vibrio cholerae, which produces the cholera toxin (CT). In addition to improving water sanitation, oral cholera vaccines have been developed to control infection. Besides, rehydration and antibiotic therapy are complementary treatment strategies for cholera. ToxT regulatory protein activates transcription of <i>CT</i> gene, which is enhanced by bicarbonate (HCO<sub>3</sub><sup>-</sup>).</p><p><strong>Areas covered: </strong>This review delves into the genomic blueprint of V. <i>cholerae</i>, which encodes for α-, β-, and γ- carbonic anhydrases (CAs). We explore how the CAs contribute to the pathogenicity of V. <i>cholerae</i> and discuss the potential of CA inhibitors in mitigating the disease's impact.</p><p><strong>Expert opinion: </strong>CA inhibitors can reduce the virulence of bacteria and control cholera. Here, we reviewed all reported CA inhibitors, noting that α-CA from V. <i>cholerae</i> (VchCAα) was the most effective inhibited enzyme compared to the β- and γ-CA families (VchCAβ and VchCAγ). Among the CA inhibitors, acyl selenobenzenesulfonamidenamides and simple/heteroaromatic sulfonamides were the best VchCA inhibitors in the nM range. It was noted that some antibacterial compounds show good inhibitory effects on all three bacterial CAs. CA inhibitors belonging to other classes may be synthesized and tested on VchCAs to harness cholera.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"623-635"},"PeriodicalIF":4.6000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Antibacterial carbonic anhydrase inhibitors targeting <i>Vibrio cholerae</i> enzymes.\",\"authors\":\"Mohammad Sadegh Gheibzadeh, Clemente Capasso, Claudiu T Supuran, Reza Zolfaghari Emameh\",\"doi\":\"10.1080/14728222.2024.2369622\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Cholera is a bacterial diarrheal disease caused by pathogen bacteria Vibrio cholerae, which produces the cholera toxin (CT). In addition to improving water sanitation, oral cholera vaccines have been developed to control infection. Besides, rehydration and antibiotic therapy are complementary treatment strategies for cholera. ToxT regulatory protein activates transcription of <i>CT</i> gene, which is enhanced by bicarbonate (HCO<sub>3</sub><sup>-</sup>).</p><p><strong>Areas covered: </strong>This review delves into the genomic blueprint of V. <i>cholerae</i>, which encodes for α-, β-, and γ- carbonic anhydrases (CAs). We explore how the CAs contribute to the pathogenicity of V. <i>cholerae</i> and discuss the potential of CA inhibitors in mitigating the disease's impact.</p><p><strong>Expert opinion: </strong>CA inhibitors can reduce the virulence of bacteria and control cholera. Here, we reviewed all reported CA inhibitors, noting that α-CA from V. <i>cholerae</i> (VchCAα) was the most effective inhibited enzyme compared to the β- and γ-CA families (VchCAβ and VchCAγ). Among the CA inhibitors, acyl selenobenzenesulfonamidenamides and simple/heteroaromatic sulfonamides were the best VchCA inhibitors in the nM range. It was noted that some antibacterial compounds show good inhibitory effects on all three bacterial CAs. CA inhibitors belonging to other classes may be synthesized and tested on VchCAs to harness cholera.</p>\",\"PeriodicalId\":12185,\"journal\":{\"name\":\"Expert Opinion on Therapeutic Targets\",\"volume\":\" \",\"pages\":\"623-635\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert Opinion on Therapeutic Targets\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/14728222.2024.2369622\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Opinion on Therapeutic Targets","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/14728222.2024.2369622","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/19 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
摘要
导言霍乱是一种由霍乱弧菌引起的细菌性腹泻疾病,霍乱弧菌会产生霍乱毒素(CT)。除了改善水质卫生外,人们还开发了口服霍乱疫苗来控制感染。此外,补液和抗生素疗法也是霍乱的辅助治疗策略。ToxT 调控蛋白可激活 CT 基因的转录,而碳酸氢盐(HCO3-)可增强 CT 基因的转录:本综述深入研究了霍乱弧菌的基因组蓝图,其中编码了 α-、β- 和 γ-碳酸酐酶(CAs)。我们探讨了CA如何对霍乱弧菌的致病性起作用,并讨论了CA抑制剂在减轻该疾病影响方面的潜力:CA抑制剂可以降低细菌的致病力,控制霍乱。在此,我们回顾了所有报道的 CA 抑制剂,注意到与 β-CA 家族和 γ-CA 家族(VchCAβ 和 VchCAγ)相比,霍乱弧菌中的α-CA(VchCAα)是最有效的抑制酶。在 CA 抑制剂中,酰基硒苯磺酰胺类和简单/异芳香族磺酰胺类是 nM 范围内最佳的 VchCA 抑制剂。我们注意到,一些抗菌化合物对所有三种细菌 CA 都有很好的抑制作用。可以合成其他类别的 CA 抑制剂,并对 VchCA 进行测试,以控制霍乱。
Introduction: Cholera is a bacterial diarrheal disease caused by pathogen bacteria Vibrio cholerae, which produces the cholera toxin (CT). In addition to improving water sanitation, oral cholera vaccines have been developed to control infection. Besides, rehydration and antibiotic therapy are complementary treatment strategies for cholera. ToxT regulatory protein activates transcription of CT gene, which is enhanced by bicarbonate (HCO3-).
Areas covered: This review delves into the genomic blueprint of V. cholerae, which encodes for α-, β-, and γ- carbonic anhydrases (CAs). We explore how the CAs contribute to the pathogenicity of V. cholerae and discuss the potential of CA inhibitors in mitigating the disease's impact.
Expert opinion: CA inhibitors can reduce the virulence of bacteria and control cholera. Here, we reviewed all reported CA inhibitors, noting that α-CA from V. cholerae (VchCAα) was the most effective inhibited enzyme compared to the β- and γ-CA families (VchCAβ and VchCAγ). Among the CA inhibitors, acyl selenobenzenesulfonamidenamides and simple/heteroaromatic sulfonamides were the best VchCA inhibitors in the nM range. It was noted that some antibacterial compounds show good inhibitory effects on all three bacterial CAs. CA inhibitors belonging to other classes may be synthesized and tested on VchCAs to harness cholera.
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.