{"title":"应对抗菌药耐药性的氟喹诺酮类药物：诺氟沙星与环丙沙星衍生物的合理设计、机理认识和比较分析。","authors":"","doi":"10.1016/j.bioorg.2024.107773","DOIUrl":null,"url":null,"abstract":"<div><p>Antimicrobial resistance poses a global health concern and develops a need to discover novel antimicrobial agents or targets to tackle this problem. Fluoroquinolone (FN), a DNA gyrase and topoisomerase IV inhibitor, has helped to conquer antimicrobial resistance as it provides flexibility to researchers to rationally modify its structure to increase potency and efficacy. This review provides insights into the rational modification of FNs, the causes of resistance to FNs, and the mechanism of action of FNs. Herein, we have explored the latest advancements in antimicrobial activities of FN analogues and the effect of various substitutions with a focus on utilizing the FN nucleus to search for novel potential antimicrobial candidates. Moreover, this review also provides a comparative analysis of two widely prescribed FNs that are ciprofloxacin and norfloxacin, explaining their rationale for their design, structure–activity relationships (SAR), causes of resistance, and mechanistic studies. These insights will prove advantageous for new researchers by aiding them in designing novel and effective FN-based compounds to combat antimicrobial resistance.</p></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Fluoroquinolones tackling antimicrobial resistance: Rational design, mechanistic insights and comparative analysis of norfloxacin vs ciprofloxacin derivatives\",\"authors\":\"\",\"doi\":\"10.1016/j.bioorg.2024.107773\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Antimicrobial resistance poses a global health concern and develops a need to discover novel antimicrobial agents or targets to tackle this problem. Fluoroquinolone (FN), a DNA gyrase and topoisomerase IV inhibitor, has helped to conquer antimicrobial resistance as it provides flexibility to researchers to rationally modify its structure to increase potency and efficacy. This review provides insights into the rational modification of FNs, the causes of resistance to FNs, and the mechanism of action of FNs. Herein, we have explored the latest advancements in antimicrobial activities of FN analogues and the effect of various substitutions with a focus on utilizing the FN nucleus to search for novel potential antimicrobial candidates. Moreover, this review also provides a comparative analysis of two widely prescribed FNs that are ciprofloxacin and norfloxacin, explaining their rationale for their design, structure–activity relationships (SAR), causes of resistance, and mechanistic studies. These insights will prove advantageous for new researchers by aiding them in designing novel and effective FN-based compounds to combat antimicrobial resistance.</p></div>\",\"PeriodicalId\":257,\"journal\":{\"name\":\"Bioorganic Chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-09-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bioorganic Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0045206824006783\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic Chemistry","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0045206824006783","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
抗菌药耐药性是一个全球健康问题，因此需要发现新型抗菌剂或靶点来解决这一问题。氟喹诺酮（FN）是一种 DNA 回旋酶和拓扑异构酶 IV 抑制剂，它为研究人员合理改造其结构以提高效力和疗效提供了灵活性，因而有助于克服抗菌药耐药性。本综述深入探讨了 FNs 的合理改造、FNs 产生抗药性的原因以及 FNs 的作用机制。在此，我们探讨了 FN 类似物抗菌活性的最新进展以及各种取代的效果，重点是利用 FN 核寻找新的潜在抗菌候选物。此外，本综述还对两种广泛使用的 FN（环丙沙星和诺氟沙星）进行了比较分析，解释了它们的设计原理、结构-活性关系（SAR）、耐药性原因和机理研究。这些见解将有助于新研究人员设计新颖、有效的 FN 类化合物来对抗抗菌药耐药性。
Fluoroquinolones tackling antimicrobial resistance: Rational design, mechanistic insights and comparative analysis of norfloxacin vs ciprofloxacin derivatives
Antimicrobial resistance poses a global health concern and develops a need to discover novel antimicrobial agents or targets to tackle this problem. Fluoroquinolone (FN), a DNA gyrase and topoisomerase IV inhibitor, has helped to conquer antimicrobial resistance as it provides flexibility to researchers to rationally modify its structure to increase potency and efficacy. This review provides insights into the rational modification of FNs, the causes of resistance to FNs, and the mechanism of action of FNs. Herein, we have explored the latest advancements in antimicrobial activities of FN analogues and the effect of various substitutions with a focus on utilizing the FN nucleus to search for novel potential antimicrobial candidates. Moreover, this review also provides a comparative analysis of two widely prescribed FNs that are ciprofloxacin and norfloxacin, explaining their rationale for their design, structure–activity relationships (SAR), causes of resistance, and mechanistic studies. These insights will prove advantageous for new researchers by aiding them in designing novel and effective FN-based compounds to combat antimicrobial resistance.
期刊介绍：
Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry.
For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature.
The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.
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