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首页> 外文学位 >Synthesis and Anti-MRSA Activity of Hydrophilic C3-Acylated N-Thiolated Beta-Lactams and N-Acyl Ciprofloxacin-N-Thiolated Beta-Lactam Hybrids.
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Synthesis and Anti-MRSA Activity of Hydrophilic C3-Acylated N-Thiolated Beta-Lactams and N-Acyl Ciprofloxacin-N-Thiolated Beta-Lactam Hybrids.

机译：亲水性C3-酰化N-硫代β-内酰胺和N-酰基环丙沙星-N-硫代β-内酰胺杂化物的合成及抗MRSA活性。

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摘要

The Turos laboratory has been working with N-thiolated β-lactams for years trying to understand the mode of action and structural features it needs to have biological activity. Over the years new data has shown promising inhibitory activity against various microbes.;In this dissertation, a review of the vast amount of work carried out on N-thiolated β-lactams in Turos laboratory has been done and their novelty, in terms of structure and mechanism has been discussed. A complete outline of our work in the discovery and ongoing development of these compounds, starting from our initial, unexpected finding of antimicrobial activity for one of the lead compounds, to a more complete understanding of their chemical and biological mode of action and potential utility as antibacterial compounds, has been provided.;Previous researches by graduate students in the Turos laboratory have shown that N-thiolated β-lactams targets Type II Fatty Acid Synthesis (FAS). In process of understanding this further, other FAS inhibiting antibiotics like Triclosan were compared to our lactams by adding excess of exogenous fatty acids. Results revealed vast differences in the MIC value of triclosan and N-thiolated β-lactams, giving an idea that there might be a different mode of action or a different target altogether.;The third chapter discusses the study of attaching hydrophilic C3 side chains like amino acids and carbohydrates on N-thiolated β-lactams while studying the influence of microbiological activity. From the study it was found that the lengthening of the side chain halts the inhibitory activity regardless of whether the side chain contains unsaturation or branching. Results showed that polar groups were not well tolerated and the inhibitory activity goes down regardless of polarity.;Finally, research on dual-action antibiotics was discussed. Antibiotics cause continuous bacterial resistance and in this aspect use of two drugs with different mode of action can call for reduction of the resistance. Herein, N-acyl ciprofloxacin and N-thiolated β-lactams were connected together via an ester linkage. Six new hybrid compounds have been synthesized successfully and tested against E. faecium, K. pneumoniae, A. baumannii, P. aeruginosa, and E. cloacae..
机译：Turos实验室多年来一直与N-硫醇化β-内酰胺一起研究，试图了解其具有生物学活性所需的作用方式和结构特征。多年来，新的数据显示出对各种微生物有抑制作用。;本论文对Turos实验室对N-硫醇化β-内酰胺的大量工作进行了综述，并就其结构方面的新颖性进行了综述。并讨论了机制。我们对这些化合物的发现和持续开发的工作的完整概述，从我们对一种先导化合物的抗菌活性的最初的，出乎意料的发现开始，到对它们的化学和生物学作用方式及其潜在用途的更全面的了解，已经提供了抗菌化合物。; Turos实验室的研究生以前的研究表明，N-硫醇化的β-内酰胺类化合物靶向II型脂肪酸合成（FAS）。在进一步了解这一点的过程中，通过添加过量的外源脂肪酸，将其他抑制FAS的抗生素（如三氯生）与我们的内酰胺进行了比较。结果表明三氯生和N-硫醇化的β-内酰胺的MIC值存在巨大差异，这表明可能存在不同的作用方式或目标不同。;第三章讨论了连接亲水性C3侧链的研究，例如氨基酸和碳水化合物对N-硫醇化β-内酰胺的影响，同时研究微生物活性的影响。从研究中发现，不管侧链是否含有不饱和基团或支链，侧链的延长都会停止抑制活性。结果表明，极性基团耐受性不强，抑制活性下降，与极性无关。最后，对双作用抗生素的研究进行了探讨。抗生素会引起持续的细菌耐药性，在这方面，使用两种作用方式不同的药物可能会导致耐药性降低。在此，N-酰基环丙沙星和N-硫醇化的β-内酰胺通过酯键连接在一起。已经成功合成了六种新的杂合化合物，并针对屎肠球菌，肺炎克雷伯菌，鲍曼不动杆菌，铜绿假单胞菌和阴沟肠杆菌进行了测试。

著录项

  • 作者

    Bhattacharya, Biplob.;

  • 作者单位

    University of South Florida.;

  • 授予单位 University of South Florida.;
  • 学科 Chemistry General.;Chemistry Organic.
  • 学位 Ph.D.
  • 年度 2012
  • 页码 227 p.
  • 总页数 227
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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