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新型抗菌剂的设计与合成

Design and Synthesis of Novel Antimicrobial Agents.

作者信息

Breijyeh Zeinab, Karaman Rafik

机构信息

Pharmaceutical Sciences Department, Faculty of Pharmacy, Al-Quds University, Jerusalem P.O. Box 20002, Palestine.

Department of Sciences, University of Basilicata, Via dell'Ateneo Lucano 10, 85100 Potenza, Italy.

出版信息

Antibiotics (Basel). 2023 Mar 22;12(3):628. doi: 10.3390/antibiotics12030628.

Abstract

The necessity for the discovery of innovative antimicrobials to treat life-threatening diseases has increased as multidrug-resistant bacteria has spread. Due to antibiotics' availability over the counter in many nations, antibiotic resistance is linked to overuse, abuse, and misuse of these drugs. The World Health Organization (WHO) recognized 12 families of bacteria that present the greatest harm to human health, where options of antibiotic therapy are extremely limited. Therefore, this paper reviews possible new ways for the development of novel classes of antibiotics for which there is no pre-existing resistance in human bacterial pathogens. By utilizing research and technology such as nanotechnology and computational methods (such as in silico and Fragment-based drug design (FBDD)), there has been an improvement in antimicrobial actions and selectivity with target sites. Moreover, there are antibiotic alternatives, such as antimicrobial peptides, essential oils, anti-Quorum sensing agents, darobactins, vitamin B6, bacteriophages, odilorhabdins, 18β-glycyrrhetinic acid, and cannabinoids. Additionally, drug repurposing (such as with ticagrelor, mitomycin C, auranofin, pentamidine, and zidovudine) and synthesis of novel antibacterial agents (including lactones, piperidinol, sugar-based bactericides, isoxazole, carbazole, pyrimidine, and pyrazole derivatives) represent novel approaches to treating infectious diseases. Nonetheless, prodrugs (e.g., siderophores) have recently shown to be an excellent platform to design a new generation of antimicrobial agents with better efficacy against multidrug-resistant bacteria. Ultimately, to combat resistant bacteria and to stop the spread of resistant illnesses, regulations and public education regarding the use of antibiotics in hospitals and the agricultural sector should be combined with research and technological advancements.

摘要

随着耐多药细菌的传播,发现用于治疗危及生命疾病的创新抗菌药物的必要性日益增加。由于许多国家抗生素可在柜台购买,抗生素耐药性与这些药物的过度使用、滥用和误用有关。世界卫生组织(WHO)确认了对人类健康危害最大的12类细菌,针对这些细菌的抗生素治疗选择极为有限。因此,本文综述了开发新型抗生素的可能新方法,这些新型抗生素对人类细菌病原体不存在预先存在的耐药性。通过利用纳米技术和计算方法(如计算机模拟和基于片段的药物设计(FBDD))等研究和技术,抗菌作用和对靶点的选择性得到了改善。此外,还有抗生素替代品,如抗菌肽、精油、抗群体感应剂、达罗巴汀、维生素B6、噬菌体、奥德罗拉菌素、18β-甘草次酸和大麻素。此外,药物重新利用(如替卡格雷、丝裂霉素C、金诺芬、喷他脒和齐多夫定)和新型抗菌剂的合成(包括内酯、哌啶醇基、糖基杀菌剂、异恶唑、咔唑、嘧啶和吡唑衍生物)代表了治疗传染病的新方法。尽管如此,前体药物(如铁载体)最近已被证明是设计新一代抗菌剂的优秀平台,这些抗菌剂对耐多药细菌具有更好的疗效。最终,为了对抗耐药细菌并阻止耐药疾病的传播,应将医院和农业部门抗生素使用的法规及公众教育与研究和技术进步相结合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c776/10045396/f0959b357d76/antibiotics-12-00628-g001.jpg

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