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各种抗菌耐药性诱导群体感应生物合成途径介导的靶点的最新突破及其抑制剂的设计。

Recent Breakthroughs in Various Antimicrobial Resistance Induced Quorum Sensing Biosynthetic Pathway Mediated Targets and Design of their Inhibitors.

机构信息

Department of Pharmaceutical Chemistry, Global Institute of Pharmaceutical Education and Research, Affiliated to Uttarakhand Technical University, Kashipur 244713, India.

Department of Chemistry, Amity University, Lucknow, India.

出版信息

Comb Chem High Throughput Screen. 2020;23(6):458-476. doi: 10.2174/1386207323666200425205808.

Abstract

OBJECTIVE

The world is under the grasp of dangerous post-antibiotics and antimicrobials attack where common infections may become untreatable, leading to premature deaths due to antimicrobial resistance (AMR). While an estimated 7,00,000 people die annually due to AMR, which is a public health threat to all communities in different parts of the world regardless of their economic status; however, this threat is serious in low- and middle-income countries having lack of sanitation and health infrastructure. The 68th World Health Assembly endorsed the Global Action Plan on antimicrobial resistance. Consequently, many countries started drafting and committing to National Action Plans against AMR. As strong as National Action Plans are in terms of prescribing rational use of antimicrobials, infection control practices, and related public health measures, without strong healthcare systems, these measures will have a limited impact on AMR in developing countries.

METHODS

The major reason for AMR is microbial quorum sensing (QS) that may strengthen the microbial community to generate inter-communication and virulence effects via quorum sensing mechanisms. Global stewardship to combat antimicrobial resistance aims to develop anti-quorum sensing compounds that can inhibit the biosynthetic pathway mediated different quorum sensing targets.

RESULTS

It may pave an effective attempt to minimize microbial quorum sensing mediated antimicrobial resistance. The present review describes QS mediated various potential target enzymes, their connection to AMR, and finds out the corresponding QS biosynthetic target inhibitors.

CONCLUSION

These potential inhibitors can be derivatized to design and develop next-generation antimicrobial agents.

摘要

目的

世界正处于后抗生素和抗菌药物的危险攻击之下,普通感染可能变得无法治疗,从而导致因抗菌药物耐药性(AMR)而提前死亡。虽然每年约有 700 万人因 AMR 而死亡,这对世界不同地区的所有社区都是一个公共卫生威胁,无论其经济状况如何;然而,对于缺乏卫生和健康基础设施的低收入和中等收入国家来说,这一威胁更为严重。第 68 届世界卫生大会通过了《抗菌素耐药性全球行动计划》。因此,许多国家开始起草并承诺执行国家抗菌素耐药性行动计划。尽管国家行动计划在规定合理使用抗菌药物、感染控制措施和相关公共卫生措施方面非常有力,但如果没有强大的医疗保健系统,这些措施对抗菌素耐药性在发展中国家的影响将是有限的。

方法

AMR 的主要原因是微生物群体感应(QS),它可能通过群体感应机制增强微生物群落的相互通讯和毒力效应。全球对抗抗菌药物耐药性的管理旨在开发能够抑制不同群体感应靶点介导的生物合成途径的抗群体感应化合物。

结果

这可能为最大限度地减少微生物群体感应介导的抗菌药物耐药性提供了有效的尝试。本综述描述了 QS 介导的各种潜在靶酶及其与 AMR 的联系,并找到了相应的 QS 生物合成靶标抑制剂。

结论

这些潜在的抑制剂可以被衍生化,以设计和开发下一代抗菌药物。

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