{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:18:54Z","timestamp":1792811934157,"version":"4.5.0"},"reference-count":150,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T00:00:00Z","timestamp":1775347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Innovation Team Project of Guangdong Provincial Department of Education","award":["2024KCXTD012"],"award-info":[{"award-number":["2024KCXTD012"]}]},{"name":"Basic Research Fund in Shenzhen Natural Science Foundation","award":["JCYJ20241202124709013"],"award-info":[{"award-number":["JCYJ20241202124709013"]}]},{"name":"Science and Technology Development Fund, Macau SAR","award":["0023\/2021\/AGJ"],"award-info":[{"award-number":["0023\/2021\/AGJ"]}]},{"award":["0023\/2021\/AGJ"],"award-info":[{"award-number":["0023\/2021\/AGJ"]}],"id":[{"id":"https:\/\/ror.org\/044vr6g03","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Antimicrobial resistance (AMR) poses a significant global health threat, with multidrug-resistant pathogens undermining the effectiveness of conventional antibiotics. Natural alkaloids, a diverse group of nitrogen-containing compounds mainly derived from plants, are gaining attention as potential antimicrobial agents due to their broad-spectrum activity, structural variety, and unique mechanisms of action. This review examines the antimicrobial properties of natural alkaloids, classifying them by chemical structure (e.g., quinoline, isoquinoline, pyridine, indole, and imidazole alkaloids). Their antibacterial, antifungal, and antiviral activities are discussed, along with the mechanisms by which they target pathogenic microorganisms, including disruption of cell walls and membranes, inhibition of protein synthesis, interference with DNA replication, and viral assembly. The review also explores the synergistic effects of alkaloids when combined with conventional antimicrobial agents. Alkaloids demonstrate potent antimicrobial activity against various pathogens. Quinoline alkaloids, such as quinine, inhibit DNA replication and damage cell membranes. Isoquinoline alkaloids like berberine and sanguinarine exhibit broad-spectrum antibacterial effects. Pyridine alkaloids, including nicotine, disrupt bacterial membranes. In fungi, alkaloids such as sanguinarine and indole derivatives prevent cell wall synthesis and spore germination. Antiviral alkaloids like lycorine target viral RNA polymerases. Additionally, alkaloids enhance the activity of traditional antibiotics by overcoming resistance. Natural alkaloids represent a promising source of antimicrobial agents with diverse mechanisms to combat AMR. Future research should focus on optimizing alkaloid structures, ensuring safety and efficacy, and exploring combination therapies to address the escalating AMR challenge.<\/jats:p>","DOI":"10.3390\/molecules31071204","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:19:32Z","timestamp":1775434772000},"page":"1204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Natural Alkaloids as Antimicrobial Agents: Mechanisms, Potentials and Challenges"],"prefix":"10.3390","volume":"31","author":[{"given":"Xi-Zhong","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Pharmacy, Shenzhen Technology University, Shenzhen 518118, China"},{"name":"School of Pharmaceutical Sciences, Shenzhen University, Shenzhen 518000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Xia","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Shenzhen Technology University, Shenzhen 518118, China"},{"name":"School of Pharmaceutical Sciences, Shenzhen University, Shenzhen 518000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Hou","sequence":"additional","affiliation":[{"name":"Nam Yue Natural Medicine Co., Ltd., Macau, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Qin","family":"Wang","sequence":"additional","affiliation":[{"name":"Nam Yue Natural Medicine Co., Ltd., Macau, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Dan","family":"He","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Shenzhen Technology University, Shenzhen 518118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie-Shu","family":"You","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Shenzhen Technology University, Shenzhen 518118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2566-3519","authenticated-orcid":false,"given":"Xun","family":"Song","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Shenzhen Technology University, Shenzhen 518118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,5]]},"reference":[{"key":"ref_1","unstructured":"Regional Committee for the Western Pacific (2019). 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