Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
Nat Prod Rep. 2020 Nov 1;37(11):1454-1477. doi: 10.1039/d0np00022a. Epub 2020 Jul 1.
Natural products have historically been a rich source of diverse chemical matter with numerous biological activities, and have played an important role in drug discovery in many areas including infectious disease. Synthetic and medicinal chemistry have been, and continue to be, important tools to realize the potential of natural products as therapeutics and as chemical probes. The formation of biofilms by bacteria in an infection setting is a significant factor in the recalcitrance of many bacterial infections, conferring increased tolerance to many antibiotics and to the host immune response, and as yet there are no approved therapeutics for combatting biofilm-based bacterial infections. Small molecules that interfere with the ability of bacteria to form and maintain biofilms can overcome antibiotic tolerance conferred by the biofilm phenotype, and have the potential to form combination therapies with conventional antibiotics. Many natural products with anti-biofilm activity have been identified from plants, microbes, and marine life, including: elligic acid glycosides, hamamelitannin, carolacton, skyllamycins, promysalin, phenazines, bromoageliferin, flustramine C, meridianin D, and brominated furanones. Total synthesis and medicinal chemistry programs have facilitated structure confirmation, identification of critical structural motifs, better understanding of mechanistic pathways, and the development of more potent, more accessible, or more pharmacologically favorable derivatives of anti-biofilm natural products.
天然产物一直是具有多种生物活性的化学物质的丰富来源，在包括传染病在内的许多领域的药物发现中发挥了重要作用。合成和药物化学一直是，并且仍然是实现天然产物作为治疗剂和化学探针的潜力的重要工具。在感染环境中，细菌形成生物膜是许多细菌感染难以治愈的一个重要因素，使细菌对许多抗生素和宿主免疫反应产生更高的耐受性，而目前还没有针对生物膜相关细菌感染的批准疗法。干扰细菌形成和维持生物膜能力的小分子可以克服生物膜表型赋予的抗生素耐受性，并有可能与传统抗生素形成联合疗法。从植物、微生物和海洋生物中已经鉴定出许多具有抗生物膜活性的天然产物，包括：elligic 酸糖苷、hamamelitannin、carolacton、skyllamycins、promysalin、phenazines、bromoageliferin、flustramine C、meridianin D 和溴代呋喃酮。全合成和药物化学计划促进了结构确证、关键结构基序的鉴定、对机制途径的更好理解，以及更有效、更易获得或更具药理优势的抗生物膜天然产物衍生物的开发。
