Amino acid-derived defense metabolites from plants: A potential source to facilitate novel antimicrobial development.
Amino acid-derived defense metabolites from plants: A potential source to facilitate novel antimicrobial development.
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DOI：
10.1016/j.jbc.2021.100438
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Hudson AO
中科院分区：
文献类型：
--
作者：
Parthasarathy A;Borrego EJ;Savka MA;Dobson RCJ;Hudson AO
几千年来，人类一直依赖植物作为药物，现代药理学继续重新检查和挖掘植物代谢物，以获得新的化合物，并指导生物活性，生物利用度和化学稳定性的改善。抗生素耐药性和病毒和寄生虫病暴露增加的关键问题激发了人们对感染性疾病药物治疗的新兴趣。在这种背景下，全球正在紧急恢复天然产物的发现，特别关注许多化学上不同的植物防御化合物，如植物抗毒素和植物预期素，它们可以对抗食草动物，微生物病原体或竞争植物。此外，“组学”、化学和异源表达系统的进步促进了植物代谢物的纯化和表征以及可能的治疗靶点的鉴定。在这篇综述中，我们描述了几种重要的氨基酸衍生的植物防御化合物，包括抗菌肽（例如，防御素、硫堇素和结素）、生物碱、非蛋白氨基酸和苯丙素类作为潜在的药物先导物，检查它们的作用机制、治疗靶点和结构-功能关系。鉴于其有效的抗细菌、抗真菌、抗寄生虫和抗病毒特性，其可以上级现有药物，植物抗毒素和植物预期素是促进抗微生物药物的合理设计和开发的极好资源。
For millennia, humanity has relied on plants for its medicines, and modern pharmacology continues to reexamine and mine plant metabolites for novel compounds and to guide improvements in biological activity, bioavailability, and chemical stability. The critical problem of antibiotic resistance and increasing exposure to viral and parasitic diseases has spurred renewed interest into drug treatments for infectious diseases. In this context, an urgent revival of natural product discovery is globally underway with special attention directed toward the numerous and chemically diverse plant defensive compounds such as phytoalexins and phytoanticipins that combat herbivores, microbial pathogens, or competing plants. Moreover, advancements in “omics,” chemistry, and heterologous expression systems have facilitated the purification and characterization of plant metabolites and the identification of possible therapeutic targets. In this review, we describe several important amino acid–derived classes of plant defensive compounds, including antimicrobial peptides (e.g., defensins, thionins, and knottins), alkaloids, nonproteogenic amino acids, and phenylpropanoids as potential drug leads, examining their mechanisms of action, therapeutic targets, and structure–function relationships. Given their potent antibacterial, antifungal, antiparasitic, and antiviral properties, which can be superior to existing drugs, phytoalexins and phytoanticipins are an excellent resource to facilitate the rational design and development of antimicrobial drugs.
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