Design, Synthesis, and Antibacterial Activity of Novel Kojic Acid-Thioether Derivatives

doi:10.6023/cjoc202604005

Chinese Journal of Organic Chemistry

ARTICLE

新型曲酸-硫醚衍生物的设计、合成及抗菌活性研究

吕洁¹, 宋佳², 阳欣燕¹, 丘栩宁¹, 李凯文¹, 袁紫亮^1,*, 任彦荣^1,*, 李停停^2,*

¹重庆第二师范学院生物与化学工程学院重庆 400067;
²贵州大学绿色农药全国重点实验室贵阳 550025

收稿日期:2026-04-02 修回日期:2026-05-29
基金资助:
重庆市科卫联合中医药科研项目(No. 2026ZYQN02), 重庆市自然科学基金创新发展联合基金项目((No. CSTB2023NSCQ-LZX0171)及重庆第二师范学院项目(No. BSRC2024070, No. 2025XJQNXZTJ05)资助.

Design, Synthesis, and Antibacterial Activity of Novel Kojic Acid-Thioether Derivatives

Lv Jie¹, Song Jia², Yang Xinyan¹, Qiu Xuning¹, Li Kaiwen¹, Yuan Ziliang^1,*, Ren Yanrong^1,*, Li Tingting^2,*

¹Department of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, China.;
²State Key Laboratory of Green Pesticide, Guizhou University, Guiyang 550025, China.

Received:2026-04-02 Revised:2026-05-29
Contact: ^*E-mail: yuan-zi-liang@outlook.com; renyr@cque.edu.cn; litt8293@163.com
Supported by:
Traditional Chinese Medicine Research Program of Chongqing Science and Health (No. 2026ZYQN023), the Chongqing Natural Science Foundation Innovation and Development Joint Fund Project (No. CSTB2023NSCQ-LZX0171), and the University-level Project of Chongqing University of Education (No. BSRC2024070, No. 2025XJQNXZTJ05).

1. .pdf(3273KB)

Abstract

To develop novel antibacterial agents against Xanthomonas oryzae pv. oryzae (Xoo), 18 new kojic acid-thioether derivatives were designed and synthesized through structural modification of kojic acid by incorporating bioactive thioether fragments. The structures of target derivatives were identified by ¹H NMR and ¹³C NMR spectroscopy, and those of fluorine-containing derivatives were additionally confirmed by ¹⁹F NMR spectroscopy. The in vitro anti-Xoo activity evaluation revealed that several derivatives (3a, 3b, 3c, 3e, 3j, and 3o) exhibited significant inhibitory activity. Compound 3c (para-bromo substituted) showed the most potent activity (EC₅₀ = 5.22 mg/L), which significantly exceeded those of the controls bismerthiazol (BT, EC₅₀ = 20.82 mg/L) and thiodiazole copper (TC, EC₅₀ = 89.77 mg/L). Structure-activity relationship analysis indicated that electron-withdrawing substituents and para-substitution on the phenyl ring are crucial for enhancing anti-Xoo activity. Molecular docking results indicated that compound 3c forms hydrogen bonds and π‑halogen interactions with key amino acid residues. These results demonstrate that compound 3c is a promising novel anti-Xoo agent.

Key words: Kojic acid-thioether derivatives, Antibacterial activity, Structure-activity relationship, Molecular docking

Cite this article

Lv Jie, Song Jia, Yang Xinyan, Qiu Xuning, Li Kaiwen, Yuan Ziliang, Ren Yanrong, Li Tingting. Design, Synthesis, and Antibacterial Activity of Novel Kojic Acid-Thioether Derivatives[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202604005.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1] NiÑO, D. O.; Ronald, P. C.; Bogdanove, A. J.Mol. Plant Pathol. 2006, 7, 303-324.
[2] Wang S.; Chen J.; Shi J.; Wang Z.; Hu D.; Song B.J. Agric. Food Chem. 2021, 69, 11804-11815.
[3] Yang T.; Zhang T.; Zhou X.; Wang P.; Gan J.; Song B.; Yang S.; Yang C.-G.J. Agric. Food Chem. 2021, 69, 7545-7553.
[4] Liu T.; Shi J.; Liu D.; Zhang D.; Song B.; Hu D.J. Agric. Food Chem. 2022, 70, 99-110.
[5] Jiang H.; Xu X.; Lv L.; Huang X.; Ahmed T.; Tian Y.; Hu S.; Chen J.; Li B.J. Agric. Food Chem. 2024, 73, 249-259.
[6] Shao J.; Zhang Z.-J.; Shi Y.; Jiang W.-Q.; Siddique F.; Chen L.; Liu G.; Zhu J.; Luo X.-F.; Liu Y.-Q.; An J.-X.; Yang C.-J.; Cui Z.-N.J. Agric. Food Chem. 2024, 72, 6988-6997.
[7] Wu S.; Jin Z.; Wang P.; Song R.; Song B.Chem. Soc. Rev. 2026, 55, 1131-1230.
[8] Mansfield J.; Genin S.; Magori S.; Citovsky V.; Sriariyanum M.; Ronald P.; Dow M. A.X.; Verdier, V.; Beer, S. V.; Machado, M. A.; Toth, I. A. N.; Salmond, G.; Foster, G. D.Mol. Plant Pathol. 2012, 13, 614-629.
[9] Liu W.; Liu J.; Triplett L.; Leach J. E.; Wang G.-L.Annu. Rev. Phytopathol. 2014, 52, 213-241.
[10] Cai L.; Cao Y.; Xu Z.; Ma W.; Zakria M.; Zou L.; Cheng Z.; Chen G.Sci. Rep. 2017, 7, 5089.
[11] Iacobellis N. S.;Lo Cantore, P.; Capasso, F.; Senatore, F.J. Agric. Food Chem. 2004, 53, 57-61.
[12] Sundin G. W.; Castiblanco L. F.; Yuan X.; Zeng Q.; Yang C. H.Mol. Plant Pathol. 2016, 17, 1506-1518.
[13] Peng F.; Liu T.; Zhu Y.; Liu F.; Cao X.; Wang Q.; Liu L.; Xue W.Pest Manag. Sci. 2022, 79, 274-283.
[14] Wightwick A. M.; Mollah M. R.; Partington D. L.; Allinson G.J. Agric. Food Chem. 2008, 56, 2457-2464.
[15] Wu Q.; Cai H.; Yuan T.; Li S.; Gan X.; Song, B. Bioorg. Med. Chem. Lett.2020, 30, 127113.
[16] Xiang J.; Liu D.; Chen J.; Hu D.; Song B.Pestic. Biochem. Physiol. 2020, 170, 104695.
[17] Batuman O.;Britt-Ugartemendia, K.; Kunwar, S.; Yilmaz, S.; Fessler, L.; Redondo, A.; Chumachenko, K.; Chakravarty, S.; Wade, T.Phytopathology 2024, 114, 885-909.
[18] Antonopoulou I.; Varriale S.; Topakas E.; Rova U.; Christakopoulos P.; Faraco V.Appl. Microbiol. Biotechnol. 2016, 100, 6519-6543.
[19] Ashooriha M.; Ahmadi R.; Ahadi H.; Emami S.Chem. Biol. Drug. Des. 2022, 100, 290-303.
[20] Emami S.; Ahmadi R.; Ahadi H.; Ashooriha M.Med. Chem. Res. 2022, 31, 1842-1861.
[21] Chib S.; Jamwal V. L.; Kumar V.; Gandhi S. G.; Saran S.Appl. Microbiol. Biotechnol. 2023, 107, 2111-2130.
[22] Saeedi M.; Eslamifar M.; Khezri K.Biomed. Pharmacother. 2019, 110, 582-593.
[23] Brtko J.Arch. Pharm. 2022, 355, e2200215.
[24] Ermis N.; Zare N.; Darabi R.; Alizadeh M.; Karimi F.; Singh J.; Shahidi S.-A.; Dragoi E. N.; Camarada M. B.; Baghayeri M.J. Food Meas. Charact. 2023, 17, 3644-3653.
[25] Uher, M. Chem. Papers 1994, 48, 282-284.
[26] Liu X.; Xia W.; Jiang Q.; Xu Y.; Yu P.J. Agric. Food Chem. 2013, 62, 297-303.
[27] Andrade G. F.;Lima, G. d. S.; Gastelois, P. L.; Assis Gomes, D.; Macedo, W. A. d. A.; de Sousa, E. M. B.Int. J. Appl. Ceram. Technol. 2019, 17, 380-391.
[28] Leitão M. M.; Gonçalves A. S.C.; Moreira, J.; Fernandes, C.; Borges, F.; Simões, M.; Borges, A.Eur. J. Med. Chem. 2025, 283, 117163.
[29] Raku T.; Tokiwa Y.Biotechnol. Lett. 2003, 25, 969-974.
[30] Faig J. J.; Moretti A.; Joseph L. B.; Zhang Y.; Nova M. J.; Smith K.; Uhrich K. E.Biomacromolecules 2017, 18, 363-373.
[31] Liu X.; Xu Y.; Zhan X.; Xie W.; Yang X.; Cui S. W.; Xia W.Int. J. Biol. Macromol. 2020, 144, 483-490.
[32] Hassan O. H.; Saad A. S.; Ghali M.Sci. Rep. 2024, 14, 21144.
[33] Ferlazzo A.;Armeli Iapichino, M. T.; Calabrese, G.; D’Accurso, G.; Fiorenza, R.; Pistarà, V.; Gulino, A.; Rescifina, A.; Patamia, V.; Floresta, G.ACS Appl. Nano Mater. 2025, 8, 16736-16747.
[34] Baláž Š.; Uher M.; Brtko J.; Veverka M.; Bransová J.; Dobias J.; Pódová M.; Buchvald J.Folia Microbiol. 1993, 38, 387-391.
[35] Hasil A.; Mehmood A.; Noureen S.; Ahmed M.J. Mol. Struct. 2020, 1216, 128295.
[36] Sereshti H.; Seraj M.; Soltani S.; Rashidi Nodeh, H.; Hossein Shojaee AliAbadi, M.; Taghizadeh, M.Microchem. J. 2022, 175, 107226.
[37] Talebi M.; Majidi K.; Bassam K.; Abdi M.; Daneshvar M.; Moayedi S. S.; Pourhesabi S.; Attarroshan M.; Boumi S.; Kabiri M.; Hosseini F. S.; Khoshneviszadeh M.; Amanlou M.J. Mol. Struct. 2022, 1268, 133707.
[38] Li P.; Yang Y.; Wang X.; Wu X.J. Heterocycl. Chem. 2021, 58, 1225-1251.
[39] Liu D.; Gao Y.; Pei H.; Ye J.; Hao H.; Zhang J.; Zhang L.J. Agric. Food Chem. 2024, 72, 18045-18055.
[40] Xiao T.; Liu A.; Liu X.; Zhong F.; Li G.; Huang Z.; Zhang Z.; Ren Y.; Li J.-S.; Liu W.Med. Chem. Res. 2024, 33, 930-943.
[41] Xu T.; Meng J.-R.; Cheng W.; Liu J.-Z.; Chu J.; Zhang Q.; Ma N.; Bai L.-P.; Guo Y.Biorg. Med. Chem. 2022, 67, 116838.
[42] Truong N. H.; Tran T. H.H.; Hoang, K. C.; Ninh, D. B.; Le, V. D.; Le, D. A.; Luu, V. C.; Siripuram, V. K.Heteroat. Chem 2023, 2023, 1-10.
[43] Wang Y.; Pu H.; Zou H.; Fu H.; Yang H.; Pan X.; Zhang H.; Liu D.; Xue W.J. Mol. Struct. 2026, 1352, 144476.
[44] Liu H.-W.; Ji Q.-T.; Ren G.-G.; Wang F.; Su F.; Wang P.-Y.; Zhou X.; Wu Z.-B.; Li Z.; Yang S.J. Agric. Food Chem. 2020, 68, 12558-12568.
[45] Wu S.; Shi J.; Chen J.; Hu D.; Zang L.; Song B.J. Agric. Food Chem. 2021, 69, 4645-4654.
[46] Calderón Villalobos, L. I. A.; Lee, S.; De Oliveira, C.; Ivetac, A.; Brandt, W.; Armitage, L.; Sheard, L. B.; Tan, X.; Parry, G.; Mao, H.; Zheng, N.; Napier, R.; Kepinski, S.; Estelle, M.Nat. Chem. Biol. 2012, 8, 477-485.
[47] Zhang M.; Zhang S.; Ling D.; Pang C.; Jin Z.; Lv W.-X.; Chi Y. R.J. Agric. Food Chem. 2025, 73, 4555-4562.

新型曲酸-硫醚衍生物的设计、合成及抗菌活性研究

Design, Synthesis, and Antibacterial Activity of Novel Kojic Acid-Thioether Derivatives

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Miao Yang, Yinjiu Zhao, Yanchuan Gong, Jie Zhang, Liang Guo. Synthesis and Antitumor Activity Study of 2,3-Substituted Tetrahydro- β-carboline Fused Diketopiperazine Derivatives [J]. Chinese Journal of Organic Chemistry, 2026, 46(8): 3089-3103.
[2]	Guiping Zhang, Changhua Ding, Yong Guo, Yao Li, Xiaosong Xue. Research Progress of Machine Learning in Surfactant Performance Prediction and Design [J]. Chinese Journal of Organic Chemistry, 2026, 46(6): 2310-2326.
[3]	Liping Dong, Jinhua Yang, Rong Fang, Xing Zhang, Xiaoqiang Zhu, Xiaobin Bi, Liang Lei. Study on the Secondary Metabolites and Antibacterial Activity of a Fungus Aspergillus sp. L06 from the Roots of Stelleropsis tianschanica (Pobed) [J]. Chinese Journal of Organic Chemistry, 2026, 46(6): 2482-2486.
[4]	Mei Dong, Guo-Qiang Lin, Ran Hong, Sha-Hua Huang, Changmin Xie. Advances in the Asymmetric Synthesis of the Potent Neurotoxin Anatoxin-a [J]. Chinese Journal of Organic Chemistry, 2026, 46(6): 2193-2206.
[5]	Min Liu, Yikun Chen, Luanyuan Tian, Haifeng Zhou, Hao Zhou, Qixing Liu. Design, Synthesis, and Activity of Novel N-2,3-Difluorophenyl Cyclobutylamine M4 AChR Positive Allosteric Modulators [J]. Chinese Journal of Organic Chemistry, 2026, 46(5): 2138-2148.
[6]	Huixian She, Qing Wang, Qin Zha, Jiaqiang Yang. Design, Synthesis and Antibacterial Activities of Isoxzoleamide Derivatives Containing Phosphonate Fragment [J]. Chinese Journal of Organic Chemistry, 2026, 46(5): 2059-2066.
[7]	Jueying Shi, Yikang Qiu, Jing Lan, Zhenyang Xu, Yi Wang, Jiaxiang Li, Youping Luo, Guolei Huang, Caijuan Zheng. Research on Secondary Metabolites from a Mangrove-Derived Fungus Penicillium janthinellum XLN32122 and Their Biological Activities [J]. Chinese Journal of Organic Chemistry, 2026, 46(2): 678-683.
[8]	Xiaochen Liu, Ying Lei, Kai Tang, Yi Lin, Changqi Ma. Progress in Molecular Structure Topology of Non-Fullerene Acceptors for Organic Solar Cells [J]. Chinese Journal of Organic Chemistry, 2026, 46(2): 399-419.
[9]	Xinyi Cui, Lifan Guo, Congxuan Ma, Yun Li, Jianhua Liang. Structural Modifications, Structure-Activity Relationships, and Total Synthesis Advances in Erythromycin Analogs against Resistant Pathogens [J]. Chinese Journal of Organic Chemistry, 2026, 46(1): 39-73.
[10]	Sai Hong, Fahong Yin, Minghui Chen, Bin Fu, Yumei Xiao, Zhaohai Qin. Study on the Synthesis and Fungicidal Activity of 1-Azolyl-1,1- diarylmethanes Containing Pyridine Ring [J]. Chinese Journal of Organic Chemistry, 2026, 46(1): 106-117.
[11]	Youxue Zhao, Xiruo Li, Luobing Meng, Chunxiu Li, Guisheng Fan, Jianhe Xu. Advances in Understanding the Substrate Promiscuity of Alcohol Dehydrogenases/Carbonyl Reductases^★ [J]. Chinese Journal of Organic Chemistry, 2025, 45(9): 3175-3185.
[12]	Haozhe Guo, Yuyin Li, Peichen Tang, Jiangli Fan. Advances in Machine Learning-Based Design of Organic Fluorescent Theranostic Molecules^★ [J]. Chinese Journal of Organic Chemistry, 2025, 45(9): 3203-3212.
[13]	Min Tang, Bin Zhang, Qiushi Wang, Chaohua Fang, Liwei Hu, Liping Guan. Design, Synthesis and Biological Activity Study of Chalcone Derivatives Based on the Inhibitory Activities of Monoamine Oxidase and Cholinesterase Containing Indole Ring and Benzothiophene Ring [J]. Chinese Journal of Organic Chemistry, 2025, 45(8): 2989-3003.
[14]	Jiaqiang Yang, Xurong Zhou, Yangmi Chen, Huixian She. Synthesis and Antibacterial Activities of Osthole Derivatives Containing Phosphonateptide Fragment [J]. Chinese Journal of Organic Chemistry, 2025, 45(4): 1306-1314.
[15]	Juanjuan Liu, Ya Gao, Guoyong Luo, Shaoping Yang. Design, Synthesis, Antitumor Activities and Molecular Docking of N-Isopimaroyl-N'-aroyl Thiosemicarbazide Derivatives [J]. Chinese Journal of Organic Chemistry, 2025, 45(12): 4497-4504.