从多酚到β-内酰胺酶：击败严重耐药性的多靶点策略
From Polyphenols to β-Lactamases: Multitarget Strategies to Defeat Severe Resistance.
摘要(中文译文)
抗菌药物耐药性（AMR）是当前全球公共卫生面临的最紧迫挑战之一，它削弱了标准抗生素治疗的有效性，并增加了发病率、死亡率和医疗成本。新抗生素的匮乏推动了针对恢复或增强现有药物有效性的替代策略的研究。天然化合物，包括多酚类、生物碱类、萜烯类和萜类化合物、抗菌肽以及微生物次级代谢产物，表现出多靶点活性，如膜破坏、外排泵抑制、生物膜抑制和群体感应干扰。与此同时，合成和半合成小分子抑制剂已被合理设计用于靶向特定的耐药决定因素，包括β-内酰胺酶、外排系统、群体感应通路以及应激诱导的突变机制，如SOS反应和DNA修复过程。这些药物作为佐剂发挥作用，在不施加强烈选择压力的情况下恢复细菌敏感性或降低细菌毒力。天然生物活性化合物与靶向小分子抑制剂的整合代表了常规抗生素的一种有前景的补充策略。需要进一步的药理学和临床研究，以将这些方法转化为抗菌药物管理计划及旨在减轻全球AMR负担的更广泛公共卫生策略中的有效工具。本叙述性综述分析了近期关于天然化合物及合成或半合成小分子抑制剂的文献，这些化合物对耐药机制具有已证实的活性。
Abstract
Antimicrobial resistance (AMR) is one of the most pressing global public health challenges, compromising the effectiveness of standard antibiotic therapies and increasing morbidity, mortality, and healthcare costs. The scarcity of new antibiotics has driven research into alternative strategies to restore or enhance the effectiveness of existing drugs. Natural compounds, including polyphenols, alkaloids, terpenes and terpenoids, antimicrobial peptides, and microbial secondary metabolites, exhibit multitarget activities such as membrane disruption, efflux pump inhibition, biofilm suppression, and quorum sensing interference. In parallel, synthetic and semi-synthetic small-molecule inhibitors have been rationally designed to target specific resistance determinants, including β-lactamases, efflux systems, quorum sensing pathways, and stress-induced mutagenesis mechanisms such as the SOS response and DNA repair processes. These agents act as adjuvants, restoring susceptibility or reducing bacterial virulence without exerting strong selective pressure. The integration of natural bioactive compounds and targeted small-molecule inhibitors represents a promising complementary strategy for conventional antibiotics. Further pharmacological and clinical investigations are required to translate these approaches into effective tools within antimicrobial stewardship programs and broader public health strategies aimed at mitigating the global burden of AMR. This narrative review analyses the recent literature on natural compounds and synthetic or semi-synthetic small-molecule inhibitors with documented activity against antimicrobial resistance mechanisms.
如何引用
AMA
Michele Nappa, Emanuela Santoro, Roberta Manente, Angelo Cianciulli, Giuseppina Moccia, Francesco De Caro, et al. From Polyphenols to β-Lactamases: Multitarget Strategies to Defeat Severe Resistance.. International journal of molecular sciences. 2026; doi:10.3390/ijms27062702.
APA
Michele Nappa, Emanuela Santoro, Roberta Manente, Angelo Cianciulli, Giuseppina Moccia, Francesco De Caro, et al (2026). From Polyphenols to β-Lactamases: Multitarget Strategies to Defeat Severe Resistance.. International journal of molecular sciences. https://doi.org/10.3390/ijms27062702
GB/T 7714
Michele Nappa, Emanuela Santoro, Roberta Manente, Angelo Cianciulli, Giuseppina Moccia, Francesco De Caro, et al. From Polyphenols to β-Lactamases: Multitarget Strategies to Defeat Severe Resistance.[J]. International journal of molecular sciences, 2026 doi:10.3390/ijms27062702.
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