含硫醚三唑的1,4-戊二烯-3-酮衍生物合成及生物活性研究

doi:10.6023/cjoc201903048

摘要/Abstract

将含硫醇的三唑引入到1,4-戊二烯-3-酮结构中, 合成一系列含硫醚三唑的1,4-戊二烯-3-酮类衍生物, 其结构通过 ¹H NMR、 ¹³C NMR、HRMS进行表征. 生物活性测试结果表明: 目标化合物对柑橘溃疡病菌(X. citri)、水稻白叶枯病菌(X. oryzae)、烟草青枯病菌(R. solanacearum)都表现出一定的抑制活性. 其中, 化合物F₄、F₆、F₁₆对柑橘溃疡病菌的EC₅₀值分别为16.3、9.9、15.9 μg/mL, 优于对照药叶枯唑(54.9 μg/mL); 化合物F₁、F₇、F₁₅对水稻白叶枯病菌的EC₅₀值分别为9.6、19.2、21.3 μg/mL, 优于对照药叶枯唑(69.3 μg/mL); 化合物F₃、F₆对烟草青枯病菌的EC₅₀值分别为14.2、14.5 μg/mL, 优于对照药叶枯唑(82.6 μg/mL). 通过扫描电镜成像探讨了目标化合物F₆对柑橘溃疡病菌(X. Citri)的可能抑菌机制.

关键词: 1,4-戊二烯-3-酮, 硫醚三唑, 生物活性, 扫描电镜

A series of novel 1,4-pentadien-3-one derivatives containing thioether triazole units were synthesized by introducing triazoles bearing thiol groups into the structures of 1,4-pentadien-3-one. The structures of the newly synthesized compounds were assigned via ¹H NMR, ¹³C NMR and HRMS. Bioassays indicated that some of the compounds showed potential antibacterial activities against X. citri, X. oryzae and R. solanacearum. Among them, compounds F₄, F₆ and F₁₆ demonstrated appreciable inhibitory effect against Xanthomonas axonopodis pv. citri, with half-maximal effective concentration (EC₅₀) values of 16.3, 9.9 and 15.9 μg/mL, which were better than commercial agent bismerthiazol (54.9 μg/mL). Compounds F₁, F₇ and F₁₅ demonstrated appreciable inhibitory effects against Xanthomonas oryzae pv. Oryzae with EC₅₀ values of 9.6, 19.2 and 21.3 μg/mL, which were better than commercial agent bismerthiazol (69.3 μg/mL). Compounds F₃ and F₆also demonstrated appreciable inhibitory effects against Ralstonia solanacearum with EC₅₀ values of 14.2 and 14.5 μg/mL, which were better than commercial agent bismerthiazol (82.6 μg/mL). The possible mechanism of the antibacterial activity of the target compound F₆ against Xanthomonas axonopodis was investigated through scanning electron microscopy.

Key words: 1,4-pentadien-3-one, thioether triazole, biological activity, scanning electron microscope

引用此文

陈英, 李普, 陈梅, 苏时军, 贺军, 张敏, 柳立伟, 薛伟. 含硫醚三唑的1,4-戊二烯-3-酮衍生物合成及生物活性研究[J]. 有机化学, 2019, 39(10): 2813-2820.

Chen Ying, Li Pu, Chen Mei, Su Shijun, He Jun, Zhang Min, Liu Liwei, Xue Wei. Syntheses and Biological Activities of 1,4-Pentadien-3-oneDerivatives Containing Thioether Triazole Moiety[J]. Chinese Journal of Organic Chemistry, 2019, 39(10): 2813-2820.

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Compound	R	X. citri		X. oryzae		R. solanacearum
Compound	R	100 μg/mL	50 μg/mL	100 μg/mL	50 μg/mL	100 μg/mL	50 μg/mL
F₁	Ph	47.0±1.6	36.5±4.0	89.5±0.9	74.3±0.1	54.5±3.4	49.8±5.3
F₂	Thiophen-2-yl	42.4±2.3	39.0±5.0	34.7±0.6	1.5±0.2	32.8±2.1	28.3±0.1
F₃	3,4-(CH₃)₂C₆H₃	57.4±4.1	41.9±2.7	17.7±0.8	10.6±1.4	75.9±1.5	62.4±0.4
F₄	4-NO₂C₆H₄	72.3±5.3	62.8±2.8	58.0±0.5	41.6±1.2	51.6±0.1	47.9±0.5
F₅	4-ClC₆H₄	68.0±0.9	52.3±2.5	60.5±1.1	48.8±0.5	48.3±2.4	35.2±1.6
F₆	4-FC₆H₄	82.5±0.2	78.6±2.9	59.0±4.7	50.6±3.0	76.8±5.4	66.3±3.5
F₇	2,4-(CH₃O)₂C₆H₃	71.3±0.9	63.5±0.4	70.0±0.4	62.9±0.9	53.2±0.6	50.0±3.2
F₈	3-NO₂C₆H₄	66.9±6.4	57.1±1.1	60.1±1.6	51.7±1.8	50.5±3.8	41.7±5.2
F₉	2-ClC₆H₄	72.6±4.3	64.1±2.2	56.2±4.7	47.6±2.6	41.6±0.9	35.2±0.5
F₁₀	4-CH₃OC₆H₄	70.9±2.9	64.5±5.4	61.7±0.9	57.4±2.6	48.3±2.5	32.4±3.5
F₁₁	4-Methylthiazol-5-yl	63.3±5.6	56.5±1.2	46.9±2.8	44.7±0.8	44.9±1.6	36.3±1.3
F₁₂	Furan-2-yl	55.3±1.3	48.1±2.5	68.6±4.2	56.7±0.2	37.4±0.7	23.2±4.8
F₁₃	3,4-(CH₃O)₂C₆H₃	38.5±4.0	25.0±1.6	66.2±0.4	60.4±3.9	54.8±1.9	42.1±1.3
F₁₄	4-BrC₆H₄	73.6±6.1	65.8±2.7	62.2±0.7	54.9±0.4	50.2±0.1	47.1±7.2
F₁₅	2,4-Cl₂C₆H₃	56.7±2.4	45.7±4.9	61.7±0.4	54.9±0.6	55.9±1.1	42.4±0.6
F₁₆	4-CH₃C₆H₄	77.4±4.0	68.7±1.4	53.0±1.9	44.6±0.6	51.0±1.8	33.9±2.3
Bismerthiazol^b	—	59.5±7.7	49.5±5.7	56.0±1.2	33.8±2.0	61.1±6.2	49.5±5.3

Compound	R	X. citri		X. oryzae		R. solanacearum
Compound	R	100 μg/mL	50 μg/mL	100 μg/mL	50 μg/mL	100 μg/mL	50 μg/mL
F₁	Ph	47.0±1.6	36.5±4.0	89.5±0.9	74.3±0.1	54.5±3.4	49.8±5.3
F₂	Thiophen-2-yl	42.4±2.3	39.0±5.0	34.7±0.6	1.5±0.2	32.8±2.1	28.3±0.1
F₃	3,4-(CH₃)₂C₆H₃	57.4±4.1	41.9±2.7	17.7±0.8	10.6±1.4	75.9±1.5	62.4±0.4
F₄	4-NO₂C₆H₄	72.3±5.3	62.8±2.8	58.0±0.5	41.6±1.2	51.6±0.1	47.9±0.5
F₅	4-ClC₆H₄	68.0±0.9	52.3±2.5	60.5±1.1	48.8±0.5	48.3±2.4	35.2±1.6
F₆	4-FC₆H₄	82.5±0.2	78.6±2.9	59.0±4.7	50.6±3.0	76.8±5.4	66.3±3.5
F₇	2,4-(CH₃O)₂C₆H₃	71.3±0.9	63.5±0.4	70.0±0.4	62.9±0.9	53.2±0.6	50.0±3.2
F₈	3-NO₂C₆H₄	66.9±6.4	57.1±1.1	60.1±1.6	51.7±1.8	50.5±3.8	41.7±5.2
F₉	2-ClC₆H₄	72.6±4.3	64.1±2.2	56.2±4.7	47.6±2.6	41.6±0.9	35.2±0.5
F₁₀	4-CH₃OC₆H₄	70.9±2.9	64.5±5.4	61.7±0.9	57.4±2.6	48.3±2.5	32.4±3.5
F₁₁	4-Methylthiazol-5-yl	63.3±5.6	56.5±1.2	46.9±2.8	44.7±0.8	44.9±1.6	36.3±1.3
F₁₂	Furan-2-yl	55.3±1.3	48.1±2.5	68.6±4.2	56.7±0.2	37.4±0.7	23.2±4.8
F₁₃	3,4-(CH₃O)₂C₆H₃	38.5±4.0	25.0±1.6	66.2±0.4	60.4±3.9	54.8±1.9	42.1±1.3
F₁₄	4-BrC₆H₄	73.6±6.1	65.8±2.7	62.2±0.7	54.9±0.4	50.2±0.1	47.1±7.2
F₁₅	2,4-Cl₂C₆H₃	56.7±2.4	45.7±4.9	61.7±0.4	54.9±0.6	55.9±1.1	42.4±0.6
F₁₆	4-CH₃C₆H₄	77.4±4.0	68.7±1.4	53.0±1.9	44.6±0.6	51.0±1.8	33.9±2.3
Bismerthiazol^b	—	59.5±7.7	49.5±5.7	56.0±1.2	33.8±2.0	61.1±6.2	49.5±5.3

Compound	R	Toxic regression equation	r	EC₅₀/(μg?mL^–1)
F₄	4-O₂NC₆H₄	y=0.7252x+4.1219	0.9871	16.3±2.5
F₅	4-ClC₆H₄	y=0.9076x+3.6020	0.9559	34.7±2.3
F₆	4-FC₆H₄	y=0.9529x+4.0511	0.9581	9.9±2.1
F₇	2,4-(CH₃O)₂C₆H₃	y=0.6956x+4.1554	0.9889	16.4±1.0
F₈	3-O₂NC₆H₄	y=0.9427x+3.5545	0.9965	34.2±2.4
F₉	2-ClC₆H₄	y=0.8344x+3.9314	0.9978	19.1±2.7
F₁₀	4-CH₃OC₆H₄	y=0.7527x+4.0683	0.9897	17.3±2.8
F₁₄	4-BrC₆H₄	y=0.8865x+3.8683	0.9899	18.9±2.8
F₁₆	4-CH₃C₆H₄	y=0.9412x+3.8669	0.9965	15.9±1.9
Bismerthiazol^a	—	y=0.8357x+3.5466	0.9876	54.9±1.4

Compound	R	Toxic regression equation	r	EC₅₀/(μg?mL^–1)
F₄	4-O₂NC₆H₄	y=0.7252x+4.1219	0.9871	16.3±2.5
F₅	4-ClC₆H₄	y=0.9076x+3.6020	0.9559	34.7±2.3
F₆	4-FC₆H₄	y=0.9529x+4.0511	0.9581	9.9±2.1
F₇	2,4-(CH₃O)₂C₆H₃	y=0.6956x+4.1554	0.9889	16.4±1.0
F₈	3-O₂NC₆H₄	y=0.9427x+3.5545	0.9965	34.2±2.4
F₉	2-ClC₆H₄	y=0.8344x+3.9314	0.9978	19.1±2.7
F₁₀	4-CH₃OC₆H₄	y=0.7527x+4.0683	0.9897	17.3±2.8
F₁₄	4-BrC₆H₄	y=0.8865x+3.8683	0.9899	18.9±2.8
F₁₆	4-CH₃C₆H₄	y=0.9412x+3.8669	0.9965	15.9±1.9
Bismerthiazol^a	—	y=0.8357x+3.5466	0.9876	54.9±1.4

Compound	R	Toxic regression equation	r	EC₅₀/(μg?mL^–1)
F₁	Ph	y=1.0838x+3.9378	0.9488	9.6±1.9
F₅	4-ClC₆H₄	y=0.7955x+3.7062	0.9066	42.3±0.5
F₇	2,4-(CH₃O)₂C₆H₃	y=0.8195x+3.9491	0.9250	19.2±0.8
F₈	3-O₂NC₆H₄	y=0.8219x+3.6715	0.9099	41.3±1.4
F₁₀	4-CH₃OC₆H₄	y=0.8897x+3.6013	0.9524	37.3±1.5
F₁₂	Furan-2-yl	y=0.9935x+3.5123	0.9899	31.4±2.2
F₁₃	3,4-(CH₃O)₂C₆H₃	y=0.9779x+3.5713	0.9402	28.9±1.4
F₁₄	4-BrC₆H₄	y=0.8431x+3.6698	0.9886	37.8±0.8
F₁₅	2,4-Cl₂C₆H₃	y=0.4375x+4.4190	0.9756	21.3±0.8
Bismerthiazol^a	—	y=2.8364x+0.5935	0.9897	69.3±2.0