1,2-苯并异噻唑-3-酮衍生物的合成及活性研究

doi:10.6023/cjoc202311021

摘要/Abstract

1,2-苯并异噻唑-3-酮(BIT)具有一定的抗菌活性, 但其抗菌谱相对较窄. 为寻找新的抗菌药物, 以BIT为先导化合物, 采用BIT-醛-醇三分子“一锅”反应, 高效地合成了17个N-取代烷氧基甲基-1,2-苯并异噻唑-3-酮衍生物. 采用密度泛函理论(DFT)进行了反应机理的研究. 测定了对细菌、真菌和农作物病原真菌的抑菌活性, 结果表明化合物对金黄色葡萄球菌和白色念珠菌均表现出较强的抑制作用, 多数化合物的最低抑菌浓度(MIC)在1~4 mg/L之间. 化合物BIT-5、BIT-9、BIT-10以及BIT-11对所测试的多种细菌、真菌均具有较高的抑制活性, 尤其是对农作物病原真菌核盘菌、假禾谷镰孢菌、禾谷镰孢菌和小麦全蚀病菌表现出很高的抑菌活性(MIC=5~10 mg/L), 具有进一步的研究价值.

关键词: 1,2-苯并异噻唑-3-酮, 衍生物, 抗菌活性

1,2-Benzisothiazol-3-one (BIT) exhibits limited antibacterial activity, prompting the search for new antibacterial drugs. In this study, BIT was used as the starting compound to synthesize 17 new N-substituted alkoxymethylbenzoisothiazolone derivatives through one-pot reaction method involving BIT, aldehyde, and alcohol. The reaction pathways were investigated using density functional theory (DFT), and the inhibitory activity of the new compounds against bacteria, fungi, and crop pathogens was evaluated. The results demonstrated that these compounds displayed strong inhibitory effects on Staphylococcus aureus and Candida albicans, with most compounds exhibiting minimum inhibitory concentrations (MIC) ranging from 1 mg/L to 4 mg/L. Compounds BIT-5, BIT-9, BIT-10, and BIT-11 exhibited high inhibitory activity against various bacteria and fungi tested, particularly against agricultural crop disease fungi such as Sclerotinia sclerotiorum, Fusarium pseudograminearum, Fusarium graminearum, and Gaeumannomyces gramims, with MIC values in the range of 5~10 mg/L, which has further research value.

Key words: 1,2-benzisothiazolin-3-one, derivative, antibacterial activity

引用此文

王利敏, 宋晓宇, 程森祥, 陈彤, 崔得运. 1,2-苯并异噻唑-3-酮衍生物的合成及活性研究[J]. 有机化学, 2024, 44(6): 1897-1906.

Limin Wang, Xiaoyu Song, Senxiang Cheng, Tong Chen, Deyun Cui. Synthesis and Activity Study of 1,2-Benzisothiazol-3-one Derivatives[J]. Chinese Journal of Organic Chemistry, 2024, 44(6): 1897-1906.

导出引用 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

分享此文

图/表 11

参考文献 20

[1]	Yang, J.-W.; Zhang, K.-Q.; Li, H.; Zhu, Y.-H. Fine Spec. Chem. 2013, 21, 41. (in Chinese)
	(杨俊伟, 张可青, 李辉, 朱永瑞, 精细与专用化学品, 2013, 21, 41.)
[2]	Gopinath, P.; Ramalingam, K.; Muraleedharan, K. M.; Karunagaran, D. Med. Chem. Commun. 2013, 4, 749.
[3]	Tiew, K. C.; Dou, D.-F.; Teramoto, T.; Lai, H.; Alliston, K. R.; Lushington, G. H.; Padmanabhan, R.; Groutas, W. C. Bioorg. Med. Chem. 2012, 20, 1213.
[4]	Lai, H.; Dou, D.-F.; Aravapalli, S.; Teramoto, T.; Lushington, G. H.; Mwania, T. M.; Alliston, K. R.; Eichhorn, D. M.; Padmanabhan, R.; Groutas, W. C. Bioorg. Med. Chem. 2013, 21, 102.
[5]	Vicini, P.; Amoretti, L.; Ballabeni, V.; Tognolini, M.; Barocelli, E. Bioorg. Med. Chem. 2000, 8, 2355.
[6]	Desai, R. C.; Dunlap, R. P.; Farrell, R. P. Bioorg. Med. Chem. Lett. 1995, 5, 105.
[7]	Song, B. Y.; Jiang, X.-X.; Liu, X.-W.; Deng, Y.; Hu, D.-Y.; Liu, P. RSC Adv. 2021, 11, 5399.
[8]	Vicini, P.; Zani, F.; Cozzini, P.; Doytchinova, I. Eur. J. Med. Chem. 2002, 37, 553. pmid: 12126774
[9]	Desai, R. C.; Dunlap, R. P.; Farrell, R. P.; Ferguson, E.; Franke, C. A.; Gordon, R.; Hlasta, D. J.; Talomie, T. G. Bioorg. Med. Chem. Lett. 1995, 5, 105.
[10]	Feng, W.; Wang, X.-H.; Song, H.-W.; Sun, Z.-F.; Wu, L.-Y.; Shi, Z.-F., Chen, G.-Y.; Lin, Q. Chemistry 2017, 80, 1133. (in Chinese)
	(冯文, 王向辉, 宋煌旺, 孙振范, 吴禄勇, 史载锋, 陈光英, 林强, 化学通报, 2017, 80, 113.)
[11]	Fiorenza, V.; Bianca, R.; Walter, P.; Luca, M.; Alessandra, M.; Alessandra, P.; Yves, G. Tetrahedron 2016, 73, 1745.
[12]	Xu, F.-L.; Lin, Q.; Yuan, W.; He, Y.-N. Synth. Commun. 2006, 36, 3135.
[13]	Xu, F.-L. M.S. Thesis, Hainan University, Haikou, 2006. (in Chinese)
	(许凤玲, 硕士论文, 海南大学, 海口, 2006.)
[14]	Xu, F.-L.; Lin, Q.; Hou, B. J. Heterocycl. Chem. 2006, 46, 320.
[15]	Wang, X.-H., You, C.-H., Lin, Q. Chin. J. Struct. Chem. 2013, 32, 1123.
[16]	Xu, F.-L.; Lin, Q., Wen, Y.; He, Y.-N. Synth. Commun. 2006, 36, 3135.
[17]	Dou, D.-F.; Alex, D.; Du, B.-F.; Tiew, K. C.; Aravapalli, S.; Mandadapu, S. R.; Calderone, R.; Groutas, W. C. Bioorg. Med. Chem. 2011, 19, 5782.
[18]	Gopinath, P.; Yadav, R. K.; Shukla, P. K.; Srivastava, K.; Puri, S. K.; Muraleedharan, K. M. Bioorg. Med. Chem. 2017, 27, 1291.
[19]	Zani, F.; Vicini, P.; Incerti, M. Eur. J. Med. Chem. 2004, 39, 135.
[20]	Cheng, T.-J.; Zhao, Y.-A.; Li, X., Lin, F., Xu, Y., Zhang, X.-L, Li, Y.; Wang, R.-X. J. Chem. Inf. Model. 2007, 47, 2140.

化合物	大肠杆菌	金黄色葡萄球菌	铜绿假单胞菌	白色念珠菌	金灰青霉	黑曲霉	绿色木霉
BIT	—	—	—	—	60	>100	20
左氧氟沙星	0.5	1	8	>128	—	—	—
BIT-1a	>128	2	>128	2	100	>100	100
BIT-2	32	1	64	2	100	>100	80
BIT-2a	>128	4	>128	4	>100	>100	>100
BIT-3	64	1	128	1	80	>100	>100
BIT-3a	>128	4	>128	8	>100	>100	>100
BIT-4	64	1	64	2	>100	>100	>100
BIT-4a	>128	4	>128	16	>100	>100	>100
BIT-5	128	2	128	2	60	60	20
BIT-5a	>128	4	>128	4	>100	>100	>100
BIT-6	>128	1	>128	2	60	>100	60
BIT-7	>128	8	128	2	80	>100	60
BIT-7a	>128	4	>128	8	>100	>100	>100
BIT-8	>128	2	>128	4	100	100	>100
BIT-9	>128	1	>128	4	80	80	100
BIT-10	>128	4	>128	2	100	100	80
BIT-11	>128	2	>128	8	80	>100	100
BIT-12	>128	1	>128	4	>100	>100	>100

化合物	大肠杆菌	金黄色葡萄球菌	铜绿假单胞菌	白色念珠菌	金灰青霉	黑曲霉	绿色木霉
BIT	—	—	—	—	60	>100	20
左氧氟沙星	0.5	1	8	>128	—	—	—
BIT-1a	>128	2	>128	2	100	>100	100
BIT-2	32	1	64	2	100	>100	80
BIT-2a	>128	4	>128	4	>100	>100	>100
BIT-3	64	1	128	1	80	>100	>100
BIT-3a	>128	4	>128	8	>100	>100	>100
BIT-4	64	1	64	2	>100	>100	>100
BIT-4a	>128	4	>128	16	>100	>100	>100
BIT-5	128	2	128	2	60	60	20
BIT-5a	>128	4	>128	4	>100	>100	>100
BIT-6	>128	1	>128	2	60	>100	60
BIT-7	>128	8	128	2	80	>100	60
BIT-7a	>128	4	>128	8	>100	>100	>100
BIT-8	>128	2	>128	4	100	100	>100
BIT-9	>128	1	>128	4	80	80	100
BIT-10	>128	4	>128	2	100	100	80
BIT-11	>128	2	>128	8	80	>100	100
BIT-12	>128	1	>128	4	>100	>100	>100