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磺胺类细菌碳酸酐酶抑制剂。

Sulfonamide inhibitors of bacterial carbonic anhydrases.

机构信息

Sezione di Scienze Farmaceutiche, NEUROFARBA Department, University of Florence, Sesto Fiorentino, Florence, Italy.

出版信息

Enzymes. 2024;55:143-191. doi: 10.1016/bs.enz.2024.06.006. Epub 2024 Jul 5.

Abstract

The increasing prevalence of antibiotic-resistant bacteria necessitates the exploration of novel therapeutic targets. Bacterial carbonic anhydrases (CAs) have been known for decades, but only in the past ten years they have garnered significant interest as drug targets to develop antibiotics having a diverse mechanism of action compared to the clinically used drugs. Significant progress has been made in the field in the past three years, with the validation in vivo of CAs from Neisseria gonorrhoeae, and vancomycin-resistant enterococci as antibiotic targets. This chapter compiles the state-of-the-art research on sulfonamide derivatives described as inhibitors of all known bacterial CAs. A section delves into the mechanisms of action of sulfonamide compounds with the CA classes identified in pathogenic bacteria, specifically α, β, and γ classes. Therefore, the inhibitory profiling of the bacterial CAs with classical and clinically used sulfonamide compounds is reported and analyzed. Another section covers various other series of sulfonamide CA inhibitors studied for the development of new antibiotics. By synthesizing current research findings, this chapter highlights the potential of sulfonamide inhibitors as a novel class of antibacterial agents and paves the way for future drug design strategies.

摘要

抗生素耐药菌的不断增加,需要探索新的治疗靶点。细菌碳酸酐酶(CA)已被人们认识了几十年,但直到过去十年,它们才作为药物靶点引起了人们的极大兴趣,因为它们的作用机制与临床应用的药物不同。在过去的三年中,该领域取得了重大进展,已在体内验证了淋病奈瑟菌和耐万古霉素肠球菌的 CA 作为抗生素靶点的作用。本章汇集了作为所有已知细菌 CA 抑制剂的磺胺衍生物的最新研究进展。其中一个部分深入探讨了磺胺类化合物与致病性细菌中 CA 类的作用机制,特别是α、β和γ类。因此,报告并分析了经典和临床应用的磺胺类化合物对细菌 CA 的抑制特性。另一个部分涵盖了为开发新抗生素而研究的各种其他系列磺胺 CA 抑制剂。通过综合当前的研究成果,本章强调了磺胺抑制剂作为一类新型抗菌药物的潜力,并为未来的药物设计策略铺平了道路。

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