Discovery of structurally diverse polyprenylated acylphloroglucinols with quorum sensing inhibitory activity from Hypericum seniawinii Maxim.

doi:10.1007/s13659-025-00520-z

Natural Products and Bioprospecting ›› 2025, Vol. 15 ›› Issue (4): 40-40.DOI: 10.1007/s13659-025-00520-z

• ORIGINAL ARTICLES • Previous Articles

Discovery of structurally diverse polyprenylated acylphloroglucinols with quorum sensing inhibitory activity from Hypericum seniawinii Maxim.

Yulin Duan^1,2, Xiaoxia Gu¹, Xincai Hao⁴, Guosheng Cao^5,6,7, Weiguang Sun¹, Changxing Qi^1,3, Yonghui Zhang¹

1. Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People's Republic of China;
2. Department of Pharmacy, Wuhan No. 1 Hospital, Wuhan, 430022, People's Republic of China;
3. Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China;
Key Laboratory of Henan Province for Drug Quality and Evaluation;
Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China;
4. Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei Engineering Technology Center for Comprehensive Utilization of Medicinal Plants, College of Pharmacy, Hubei University of Medicine, Shiyan, 442000, People's Republic of China;
5. College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, People's Republic of China;
6. Hubei Shizhen Laboratory, Wuhan, 430065, People's Republic of China;
7. Key Laboratory of Traditional Chinese Medicine Resource and Compound PrescriptionMinistry of Education, Hubei University of Chinese Medicine, Wuhan, 430065, People's Republic of China

Received:2025-03-06 Accepted:2025-05-13 Online:2025-06-19 Published:2025-08-23
Supported by:
This work was financially supported by the National Key Research and Development Program of China (2021YFA0910500); National Natural Science Foundation of China (Nos. 32470422 and 32300335); the National Natural Science Foundation of Hubei Province (2023AFB791 and 2023AFB530); Knowledge Innovation Project of Wuhan Science and Technology Bureau (2023020201020534); Natural Science Foundation of Wuhan (2024040801020205); the Science and Technology Major Project of Hubei Province (2021ACA012); the National Key Research and Development Program (No.2023YFC2307004); the open foundation of Key Laboratory of Ethnomedicine (Minzu University of China), Ministry of Education (No. KLEM-KF202402); the open foundation of Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education (RDZH2024001); the open foundation of Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine) (WDCM2024002); the Fundamental Research Funds for the Central Universities (HUST: 2023JYCXJJ058).

Discovery of structurally diverse polyprenylated acylphloroglucinols with quorum sensing inhibitory activity from Hypericum seniawinii Maxim.

Yulin Duan^1,2, Xiaoxia Gu¹, Xincai Hao⁴, Guosheng Cao^5,6,7, Weiguang Sun¹, Changxing Qi^1,3, Yonghui Zhang¹

1. Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People's Republic of China;
2. Department of Pharmacy, Wuhan No. 1 Hospital, Wuhan, 430022, People's Republic of China;
3. Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China;
Key Laboratory of Henan Province for Drug Quality and Evaluation;
Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China;
4. Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei Engineering Technology Center for Comprehensive Utilization of Medicinal Plants, College of Pharmacy, Hubei University of Medicine, Shiyan, 442000, People's Republic of China;
5. College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, People's Republic of China;
6. Hubei Shizhen Laboratory, Wuhan, 430065, People's Republic of China;
7. Key Laboratory of Traditional Chinese Medicine Resource and Compound PrescriptionMinistry of Education, Hubei University of Chinese Medicine, Wuhan, 430065, People's Republic of China

通讯作者: Guosheng Cao, E-mail:caoguosheng2006@163.com;Weiguang Sun, E-mail:sunweiguang@hust.edu.cn;Changxing Qi, E-mail:qichangxing@hust.edu.cn;Yonghui Zhang, E-mail:zhangyh@mails.tjmu.edu.cn
基金资助:
This work was financially supported by the National Key Research and Development Program of China (2021YFA0910500); National Natural Science Foundation of China (Nos. 32470422 and 32300335); the National Natural Science Foundation of Hubei Province (2023AFB791 and 2023AFB530); Knowledge Innovation Project of Wuhan Science and Technology Bureau (2023020201020534); Natural Science Foundation of Wuhan (2024040801020205); the Science and Technology Major Project of Hubei Province (2021ACA012); the National Key Research and Development Program (No.2023YFC2307004); the open foundation of Key Laboratory of Ethnomedicine (Minzu University of China), Ministry of Education (No. KLEM-KF202402); the open foundation of Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education (RDZH2024001); the open foundation of Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine) (WDCM2024002); the Fundamental Research Funds for the Central Universities (HUST: 2023JYCXJJ058).

Abstract

Abstract: Four previously undescribed polyprenylated acylphloroglucinols, hyperisenins A–D (1–4), along with two known analogues (5 and 6), were obtained from the aerial part of Hypericum seniawinii Maxim. Compounds 1 and 2 were two highly degraded polyprenylated acylphloroglucinols with a cyclohexanone-monocyclic skeleton, while compound 3 was the first example of O-prenylated acylphloroglucinols with a 6/6/6 ring system. Their structures were identified by analyzing NMR, HRESIMS data, and quantum chemical calculations. The biosynthetic pathway of 1 and 2 might originate from bicyclic polyprenylated acylphloroglucinols via a series of complex retro-Claisen, keto-enol tautomerism, and intramolecular cyclization. The bioassay results showed that 4 exhibited quorum sensing inhibitory activity against Pseudomonas aeruginosa, which could decrease the activation of the rhl system, and significantly reduce rhamnolipid levels at a concentration of 100 μM, and the mechanism might be the ability to bind 4 to lasR and pqsR.

Key words: Polyprenylated Acylphloroglucinols, Hypericum seniawinii Maxim., Quorum sensing inhibitory, Pseudomonas aeruginosa

摘要： Four previously undescribed polyprenylated acylphloroglucinols, hyperisenins A–D (1–4), along with two known analogues (5 and 6), were obtained from the aerial part of Hypericum seniawinii Maxim. Compounds 1 and 2 were two highly degraded polyprenylated acylphloroglucinols with a cyclohexanone-monocyclic skeleton, while compound 3 was the first example of O-prenylated acylphloroglucinols with a 6/6/6 ring system. Their structures were identified by analyzing NMR, HRESIMS data, and quantum chemical calculations. The biosynthetic pathway of 1 and 2 might originate from bicyclic polyprenylated acylphloroglucinols via a series of complex retro-Claisen, keto-enol tautomerism, and intramolecular cyclization. The bioassay results showed that 4 exhibited quorum sensing inhibitory activity against Pseudomonas aeruginosa, which could decrease the activation of the rhl system, and significantly reduce rhamnolipid levels at a concentration of 100 μM, and the mechanism might be the ability to bind 4 to lasR and pqsR.

关键词: Polyprenylated Acylphloroglucinols, Hypericum seniawinii Maxim., Quorum sensing inhibitory, Pseudomonas aeruginosa

Yulin Duan, Xiaoxia Gu, Xincai Hao, Guosheng Cao, Weiguang Sun, Changxing Qi, Yonghui Zhang. Discovery of structurally diverse polyprenylated acylphloroglucinols with quorum sensing inhibitory activity from Hypericum seniawinii Maxim.[J]. Natural Products and Bioprospecting, 2025, 15(4): 40-40.

References

[1] Hutchings MI, Truman AW, Wilkinson B. Antibiotics: past, present and future. Curr Opin Microbiol. 2019;51:72-80.
[2] de la Fuente-Nunez C, Cesaro A, Hancock REW. Antibiotic failure: beyond antimicrobial resistance. Drug Resist Updates. 2023;71:101012-21.
[3] Okeke IN, de Kraker MEA, Van Boeckel TP, Kumar CK, Schmitt H, Gales AC, Bertagnolio S, Sharland M, Laxminarayan R. The scope of the antimicrobial resistance challenge. Lancet. 2024;403(10442):2426-38.
[4] Ho CS, Wong CTH, Aung TT, Lakshminarayanan R, Mehta JS, Rauz S, McNally A, Kintses B, Peacock SJ, de la Fuente-Nunez C, Hancock REW, Ting DSJ. Antimicrobial resistance: a concise update. Lancet Microbe. 2025;6(1):100947-60.
[5] Antimicrobial Resistance C. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022;399(10325):629-55.
[6] Morrison L, Zembower TR. Antimicrobial resistance. Gastrointest Endosc Clin N Am. 2020;30(4):619-35.
[7] Vashistha A, Sharma N, Nanaji Y, Kumar D, Singh G, Barnwal RP, Yadav AK. Quorum sensing inhibitors as therapeutics: bacterial biofilm inhibition. Bioorg Chem. 2023;136:106551-70.
[8] Papenfort K, Bassler BL. Quorum sensing signal-response systems in Gram-negative bacteria. Nat Rev Microbiol. 2016;14(9):576-88.
[9] Mukherjee S, Bassler BL. Bacterial quorum sensing in complex and dynamically changing environments. Nat Rev Microbiol. 2019;17(6):371-82.
[10] Azimi S, Klementiev AD, Whiteley M, Diggle SP. Bacterial quorum sensing during infection. Annu Rev Microbiol. 2020;74(1):201-19.
[11] Maiga A, Ampomah-Wireko M, Li H, Fan Z, Lin Z, Zhen H, Kpekura S, Wu C. Multidrug-resistant bacteria quorum-sensing inhibitors: a particular focus on Pseudomonas aeruginosa. Eur J Med Chem. 2025;281:117008-31.
[12] Whiteley M, Diggle SP, Greenberg EP. Progress in and promise of bacterial quorum sensing research. Nature. 2017;551(7680):313-20.
[13] Kalia VC, Patel SKS, Kang YC, Lee J-K. Quorum sensing inhibitors as antipathogens: biotechnological applications. Biotechnol Adv. 2019;37(1):68-90.
[14] Defoirdt T. Quorum-sensing systems as targets for antivirulence therapy. Trends Microbiol. 2018;26(4):313-28.
[15] Newman DJ, Cragg GM. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J Nat Prod. 2020;83(3):770-803.
[16] Lewis K, Lee RE, Brötz-Oesterhelt H, Hiller S, Rodnina MV, Schneider T, Weingarth M, Wohlgemuth I. Sophisticated natural products as antibiotics. Nature. 2024;632(8023):39-49.
[17] Teplitski M, Robinson JB, Bauer WD. Plants secrete substances that mimic bacterial N-Acyl homoserine lactone signal activities and affect population density-dependent behaviors in associated bacteria. Mol Plant-Microbe In. 2000;13(6):637-48.
[18] Xu S, Kang A, Tian Y, Li X, Qin S, Yang R, Guo Y. Plant flavonoids with antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA). ACS Infect Dis. 2024;10(9):3086-97.
[19] Schiavone BI, Rosato A, Marilena M, Gibbons S, Bombardelli E, Verotta L, Franchini C, Corbo F. Biological evaluation of hyperforin and its hydrogenated analogue on bacterial growth and biofilm production. J Nat Prod. 2013;76(9):1819-23.
[20] Guttroff C, Baykal A, Wang H, Popella P, Kraus F, Biber N, Krauss S, Gotz F, Plietker B. Polycyclic polyprenylated acylphloroglucinols: an emerging class of non-peptide-based MRSA- and VRE-active antibiotics. Angew Chem Int Ed. 2017;56(50):15852-6.
[21] Deryabin D, Galadzhieva A, Kosyan D, Duskaev G. Plant-derived inhibitors of AHL-mediated quorum sensing in bacteria: modes of action. Int J Mol Sci. 2019;20(22):5588-609.
[22] Norizan S, Yin W-F, Chan K-G. Caffeine as a potential quorum sensing inhibitor. Sensors. 2013;13(4):5117-29.
[23] Zhou J-W, Luo H-Z, Jiang H, Jian T-K, Chen Z-Q, Jia A-Q. Hordenine: a novel quorum sensing inhibitor and antibiofilm agent against Pseudomonas aeruginosa. J Agric Food Chem. 2018;66(7):1620-8.
[24] Jakobsen TH, Bragason SK, Phipps RK, Christensen LD, van Gennip M, Alhede M, Skindersoe M, Larsen TO, Høiby N, Bjarnsholt T, Givskov M. Food as a source for quorum sensing inhibitors: Iberin from horseradish revealed as a quorum sensing inhibitor of Pseudomonas aeruginosa. Appl Environ Microbiol. 2012;78(7):2410-21.
[25] Lan X, Gu X, Zhang Y, Hu H, Shi Z, Xiong C, Huang X, Song B, Qiao Y, Sun W, Qi C, Zhang Y. Discovery of quorum sensing inhibitors against Pseudomonas aeruginosa from Aspergillus sp. NB12. Bioorg Chem. 2025;156:108230-40.
[26] Zhang R, Ji Y, Zhang X, Kennelly EJ, Long C. Ethnopharmacology of Hypericum species in China: a comprehensive review on ethnobotany, phytochemistry and pharmacology. J Ethnopharmacol. 2020;254:112686-97.
[27] Xia J, Hu B, Qian M, Zhang J, Wu L. Benzophenone Rhamnosides and Chromones from Hypericum seniawinii Maxim. Molecules. 2022;27(20):7056-65.
[28] Yang XW, Grossman RB, Xu G. Research progress of polycyclic polyprenylated acylphloroglucinols. Chem Rev. 2018;118(7):3508-58.
[29] Xie S, Zhou Y, Tan X, Sun W, Duan Y, Feng H, Sun L, Guo Y, Shi Z, Hao X, Chen G, Qi C, Zhang Y, Norwilsonnol A. an immunosuppressive polycyclic polyprenylated acylphloroglucinol with a spiro[5-oxatricyclododecane-[6.4.0.0^3,7]dodecane-6',1-1',2'-dioxane] system from Hypericum wilsonii. Org Chem Front. 2021;8(10):2280-6.
[30] Sun H, Wang J, Zhen B, Wang X, Suo X, Lin M, Jiang J, Ji T. Polycyclic polyprenylated acylphloroglucinol derivatives from Hypericum pseudohenryi. Phytochemistry. 2021;187:112761-8.
[31] Guo Y, Tong Q, Zhang N, Duan X, Cao Y, Zhu H, Xie S, Yang J, Zhang J, Liu Y, Xue Y, Zhang Y. Highly functionalized cyclohexanone-monocyclic polyprenylated acylphloroglucinols from Hypericum perforatum induce leukemia cell apoptosis. Org Chem Front. 2019;6(6):817-24.
[32] Duan YL, Deng YF, Bu PF, Xie S, Guo Y, Shi Z, Guo Y, Cao Y, Qi C, Zhang Y. Discovery of nor-bicyclic polyprenylated acylphloroglucinols possessing diverse architectures with anti-hepatoma activities from Hypericum patulum. Bioorg Chem. 2021;111:104902-12.
[33] Fobofou SA, Franke K, Sanna G, Porzel A, Bullita E, La Colla P, Wessjohann LA. Isolation and anticancer, anthelminthic, and antiviral (HIV) activity of acylphloroglucinols, and regioselective synthesis of empetrifranzinans from Hypericum roeperianum. Bioorg Med Chem. 2015;23(19):6327-34.
[34] Zeng YR, Li YN, Lou HY, Jian JY, Gu W, Huang LJ, Du GH, Yuan CM, Hao XJ. Polycyclic polyprenylated acylphloroglucinol derivatives with neuroprotective effects from Hypericum monogynum. J Asian Nat Prod Res. 2021;23(1):73-81.
[35] Seo E-K, Wani MC, Wall ME, Navarro H, Mukherjee R, Farnsworth NR, Kinghorn AD. New bioactive aromatic compounds from Vismia guianensis. Phytochemistry. 2000;55(1):35-42.
[36] Duan Y, Guo Y, Deng Y, Bu P, Shi Z, Cao Y, Zhang Y, Hu H, Sun W, Qi C, Zhang Y, Norprzewalsone A. a Rearranged Polycyclic Polyprenylated Acylphloroglucinol with a Spiro[cyclopentane-1,3’-tricyclo[7.4.0.0.^1,6]tridecane] Core from Hypericum przewalskii. J Org Chem. 2022;87(10):6824-31.
[37] Duan Y, Sun W, Li Y, Shi Z, Li L, Zhang Y, Huang K, Zhang Z, Qi C, Zhang Y. Spirohypertones A and B as potent antipsoriatics: Tumor necrosis factor-α inhibitors with unprecedented chemical architectures. Acta Pharm Sin B. 2024;14(6):2646-56.
[38] Lee J, Zhang L. The hierarchy quorum sensing network in Pseudomonas aeruginosa. Protein Cell. 2015;6(1):26-41.

Discovery of structurally diverse polyprenylated acylphloroglucinols with quorum sensing inhibitory activity from Hypericum seniawinii Maxim.

Discovery of structurally diverse polyprenylated acylphloroglucinols with quorum sensing inhibitory activity from Hypericum seniawinii Maxim.

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