含磺酰胺结构的1,3,4-噁二唑砜类化合物的设计、合成及抗菌活性研究

doi:10.6023/cjoc202204068

摘要/Abstract

为了寻找新型抗菌剂, 采用活性亚结构拼接, 设计合成了23个含磺酰胺结构的1,3,4-噁二唑砜类化合物, 并对其抗菌活性进行了测试. 在100 μg/mL浓度下, 大多数化合物对水稻细菌性条斑病菌(Xanthomonas oryzae pv. oryzicola)和水稻白叶枯病菌(Xanthomonas oryzae pv. oryzae)表现出优异的离体抗菌活性. 除N-((5-(丙基磺酰基)-1,3,4-噁二唑-2-基)甲基)-4-(三氟甲基)苯磺酰胺(18)外, 所有化合物对水稻细菌性条斑病菌的半数有效浓度(EC₅₀)值为1.3~22.5 μg/mL, 所有化合物对水稻白叶枯病菌的EC₅₀为1.1~32.7 μg/mL, 均优于对照药剂叶枯唑(84.1和71.4 µg/mL)和噻菌酮(122.1和84.0 µg/mL). 此外, 4-氟-N-((5-(甲基磺酰基)-1,3,4-噁二唑-2-基)甲基)苯磺酰胺(4)可以通过抑制胞外多糖(EPS)的产生、生物膜的形成以及改变细胞膜的通透性和细胞表面形态, 从而抑制水稻细菌性条斑病菌和水稻白叶枯病菌的正常生长.

关键词: 磺酰胺, 1,3,4-噁二唑, 合成, 抗菌活性, 生理生化

To discover new antibacterial agents, twenty-three 1,3,4-oxadiazolsulfone compounds containing a sulfonamide structure were designed and synthesized by active substructure splicing, and their antibacterial activities were tested. Most of the compounds exhibited excellent in vitro antibacterial activity against Xanthomonas oryzae pv. oryzicola (Xoc) and Xanthomonas oryzae pv. oryzae (Xoo) at a concentration of 100 µg/mL. Except for N-((5-(propylsulfonyl)-1,3,4-oxadiazo- 2-yl)methyl)-4-(trifluoromethyl)benzenesulfonamide (18), the median effective concentration (EC₅₀) values of other compounds against Xoc were 1.3~22.5 µg/mL, and the EC₅₀ of all compounds against Xoo were 1.1~32.7 µg/mL, which were better than the control agents bismerthiazol (84.1 and 71.4 µg/mL) and thiodiazole copper (122.1 and 84.0 µg/mL). In addition, 4-fluoro-N-((5-(methylsulfonyl)-1,3,4-oxadiazole-2-yl)methyl)benzenesulfonamide (4) can inhibit the growth of Xoc and Xoo by inhibiting the production of exopolysaccharide (EPS) and the formation of biofilm, changing the permeability of cell membrane and cell surface morphology.

Key words: sulfonamide, 1,3,4-oxadiazole, synthesis, antibacterial activity, physiology and biochemistry

引用此文

陈艺方, 罗鑫, 王余, 邢志富, 彭菊, 陈吉祥. 含磺酰胺结构的1,3,4-噁二唑砜类化合物的设计、合成及抗菌活性研究[J]. 有机化学, 2023, 43(1): 274-284.

Yifang Chen, Xin Luo, Yu Wang, Zhifu Xing, Ju Peng, Jixiang Chen. Design, Synthesis and Antibacterial Activity of 1,3,4-Oxadiazole Sufones Containing Sulfonamide Structure[J]. Chinese Journal of Organic Chemistry, 2023, 43(1): 274-284.

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参考文献 28

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Compd.	Inhibition rate/%				EC₅₀/(µg•mL^–1)
Compd.	100 µg/mL	50 µg/mL	20 µg/mL	10 µg/mL	EC₅₀/(µg•mL^–1)
1	98.5±0.6	98.3±0.4	97.4±0.5	93.7±0.6	2.7±0.2
2	99.1±0.2	98.8±0.2	98.1±0.6	97.5±0.8	1.9±0.3
3	98.5±0.4	98.3±0.2	97.5±0.3	96.3±0.4	2.3±0.3
4	98.8±0.3	98.6±0.2	98.4±0.5	97.5±0.2	1.1±0.1
5	98.6±0.3	98.3±0.5	98.1±0.3	96.7±0.4	1.9±0.1
6	98.6±0.6	98.4±0.1	98.5±0.4	97.4±0.5	2.1±0.1
7	98.7±0.6	98.4±0.1	97.3±0.6	96.0±0.5	1.4±0.2
8	98.7±0.5	98.2±0.3	98.4±0.8	95.2±0.3	1.7±0.2
9	99.6±0.3	99.4±0.8	98.3±0.2	94.1±4.0	2.0±0.2
10	99.1±0.8	98.4±0.5	97.6±0.6	93.2±0.6	1.8±0.2
11	98.8±0.1	98.6±0.1	97.2±0.1	96.2±0.4	2.2±0.1
12	99.4±0.7	98.9±0.6	97.4±0.6	93.7±1.1	2.6±0.1
13	98.7±0.2	98.6±0.2	98.1±0.5	97.4±0.7	1.5±0.3
14	98.7±0.5	98.3±0.2	97.1±0.3	95.0±1.3	1.8±0.2
15	98.6±0.1	98.5±0.3	89.2±1.2	76.9±2.3	5.5±0.5
16	98.7±0.2	98.7±0.4	94.7±0.6	90.9±0.7	2.6±0.1
17	98.9±0.7	98.3±0.3	95.4±1.5	78.5±2.1	4.2±0.3
18	84.0±1.9	76.2±1.3	45.6±1.4	30.2±2.4	32.7±1.2
19	98.7±0.2	89.8±1.0	80.3±3.2	47.0±4.1	8.3±0.4
20	92.2±2.7	85.7±0.8	47.6±2.6	28.4±2.3	18.7±1.2
21	98.1±1.2	96.2±0.4	97.9±0.6	97.3±1.7	1.2±0.1
Compd.	Inhibition rate/%				EC₅₀/(µg•mL^–1)
Compd.	100 µg/mL	50 µg/mL	20 µg/mL	10 µg/mL	EC₅₀/(µg•mL^–1)
22	96.7±2.3	96.0±3.0	94.2±0.3	91.6±0.6	2.3±0.2
23	95.2±1.1	91.5±1.2	97.8±0.5	86.8±0.7	2.4±0.1
BT^a	62.2±1.8	43.5±2.3	—	—	71.4±3.9
TC^b	56.2±1.1	26.9±4.3	—	—	84.0±3.1
JHXJZ^c	99.2±0.3	98.7±0.4	94.9±1.5	81.9±2.3	2.1±0.2

Compd.	Inhibition rate/%				EC₅₀/(µg•mL^–1)
Compd.	100 µg/mL	50 µg/mL	20 µg/mL	10 µg/mL	EC₅₀/(µg•mL^–1)
1	98.5±0.6	98.3±0.4	97.4±0.5	93.7±0.6	2.7±0.2
2	99.1±0.2	98.8±0.2	98.1±0.6	97.5±0.8	1.9±0.3
3	98.5±0.4	98.3±0.2	97.5±0.3	96.3±0.4	2.3±0.3
4	98.8±0.3	98.6±0.2	98.4±0.5	97.5±0.2	1.1±0.1
5	98.6±0.3	98.3±0.5	98.1±0.3	96.7±0.4	1.9±0.1
6	98.6±0.6	98.4±0.1	98.5±0.4	97.4±0.5	2.1±0.1
7	98.7±0.6	98.4±0.1	97.3±0.6	96.0±0.5	1.4±0.2
8	98.7±0.5	98.2±0.3	98.4±0.8	95.2±0.3	1.7±0.2
9	99.6±0.3	99.4±0.8	98.3±0.2	94.1±4.0	2.0±0.2
10	99.1±0.8	98.4±0.5	97.6±0.6	93.2±0.6	1.8±0.2
11	98.8±0.1	98.6±0.1	97.2±0.1	96.2±0.4	2.2±0.1
12	99.4±0.7	98.9±0.6	97.4±0.6	93.7±1.1	2.6±0.1
13	98.7±0.2	98.6±0.2	98.1±0.5	97.4±0.7	1.5±0.3
14	98.7±0.5	98.3±0.2	97.1±0.3	95.0±1.3	1.8±0.2
15	98.6±0.1	98.5±0.3	89.2±1.2	76.9±2.3	5.5±0.5
16	98.7±0.2	98.7±0.4	94.7±0.6	90.9±0.7	2.6±0.1
17	98.9±0.7	98.3±0.3	95.4±1.5	78.5±2.1	4.2±0.3
18	84.0±1.9	76.2±1.3	45.6±1.4	30.2±2.4	32.7±1.2
19	98.7±0.2	89.8±1.0	80.3±3.2	47.0±4.1	8.3±0.4
20	92.2±2.7	85.7±0.8	47.6±2.6	28.4±2.3	18.7±1.2
21	98.1±1.2	96.2±0.4	97.9±0.6	97.3±1.7	1.2±0.1
Compd.	Inhibition rate/%				EC₅₀/(µg•mL^–1)
Compd.	100 µg/mL	50 µg/mL	20 µg/mL	10 µg/mL	EC₅₀/(µg•mL^–1)
22	96.7±2.3	96.0±3.0	94.2±0.3	91.6±0.6	2.3±0.2
23	95.2±1.1	91.5±1.2	97.8±0.5	86.8±0.7	2.4±0.1
BT^a	62.2±1.8	43.5±2.3	—	—	71.4±3.9
TC^b	56.2±1.1	26.9±4.3	—	—	84.0±3.1
JHXJZ^c	99.2±0.3	98.7±0.4	94.9±1.5	81.9±2.3	2.1±0.2

Compd.	Inhibition rate/%				EC₅₀/(µg•mL^–1)
Compd.	100 µg/mL	50 µg/mL	20 µg/mL	10 µg/mL	EC₅₀/(µg•mL^–1)
1	98.7±0.4	98.3±0.7	94.9±0.6	67.9±1.7	4.5±0.3
2	98.7±0.6	97.7±1.5	95.5±0.7	88.7±1.5	2.9±0.2
3	99.0±0.3	97.5±1.3	95.3±1.3	70.1±0.9	8.4±0.1
4	98.8±0.4	96.6±0.2	97.4±0.5	96.9±0.3	1.3±0.2
5	99.1±0.1	98.7±0.5	96.3±0.4	95.5±0.7	4.0±0.2
6	98.5±0.6	98.4±0.4	95.7±0.5	71.9±2.4	6.9±0.5
7	99.3±0.6	98.0±0.5	94.6±0.6	89.2±1.1	3.1±0.3
8	98.4±0.8	98.2±0.1	95.0±0.8	90.1±0.4	4.3±0.4
9	98.7±0.2	98.0±1.0	93.2±0.4	88.0±1.1	4.6±0.2
10	98.6±0.6	97.2±0.9	96.6±0.4	92.2±0.7	2.4±0.3
11	99.2±0.1	98.4±0.5	94.6±0.3	88.8±1.2	4.1±0.3
12	98.1±0.8	97.2±1.6	95.1±1.8	86.2±0.6	4.5±0.3
13	99.1±0.7	97.5±0.7	98.4±0.7	90.5±0.6	2.8±0.6
14	99.1±0.2	96.0±1.2	94.8±0.2	76.0±1.3	5.2±0.3
15	99.2±0.2	98.6±0.4	95.0±0.4	84.9±0.9	5.3±0.4
16	97.1±1.9	94.7±2.2	94.7±0.5	89.8±0.6	4.8±0.3
17	98.3±1.6	97.3±1.1	92.6±1.7	61.3±3.1	7.0±0.3
18	42.2±2.9	27.2±6.9	—	—	99.0±8.9
19	99.5±0.6	98.8±0.3	83.8±2.7	48.9±3.6	8.9±0.7
20	93.5±2.1	63.8±2.7	47.5±2.4	24.1±2.3	22.5±3.4
21	99.1±0.2	97.5±0.8	96.5±1.2	93.7±1.3	2.1±0.3
22	98.9±0.4	97.7±0.2	92.5±0.6	62.5±0.9	6.1±0.6
23	96.8±1.5	90.8±0.3	91.3±1.1	62.9±0.7	7.3±1.4
BT^a	52.6±1.5	29.8±2.3	—	—	84.1±6.5
TC^b	38.5±5.2	27.7±6.6	—	—	122.1±9.5
JHXJZ^c	97.0±0.2	96.7±0.2	96.1±0.2	54.9±1.5	7.9±0.8

Compd.	Inhibition rate/%				EC₅₀/(µg•mL^–1)
Compd.	100 µg/mL	50 µg/mL	20 µg/mL	10 µg/mL	EC₅₀/(µg•mL^–1)
1	98.7±0.4	98.3±0.7	94.9±0.6	67.9±1.7	4.5±0.3
2	98.7±0.6	97.7±1.5	95.5±0.7	88.7±1.5	2.9±0.2
3	99.0±0.3	97.5±1.3	95.3±1.3	70.1±0.9	8.4±0.1
4	98.8±0.4	96.6±0.2	97.4±0.5	96.9±0.3	1.3±0.2
5	99.1±0.1	98.7±0.5	96.3±0.4	95.5±0.7	4.0±0.2
6	98.5±0.6	98.4±0.4	95.7±0.5	71.9±2.4	6.9±0.5
7	99.3±0.6	98.0±0.5	94.6±0.6	89.2±1.1	3.1±0.3
8	98.4±0.8	98.2±0.1	95.0±0.8	90.1±0.4	4.3±0.4
9	98.7±0.2	98.0±1.0	93.2±0.4	88.0±1.1	4.6±0.2
10	98.6±0.6	97.2±0.9	96.6±0.4	92.2±0.7	2.4±0.3
11	99.2±0.1	98.4±0.5	94.6±0.3	88.8±1.2	4.1±0.3
12	98.1±0.8	97.2±1.6	95.1±1.8	86.2±0.6	4.5±0.3
13	99.1±0.7	97.5±0.7	98.4±0.7	90.5±0.6	2.8±0.6
14	99.1±0.2	96.0±1.2	94.8±0.2	76.0±1.3	5.2±0.3
15	99.2±0.2	98.6±0.4	95.0±0.4	84.9±0.9	5.3±0.4
16	97.1±1.9	94.7±2.2	94.7±0.5	89.8±0.6	4.8±0.3
17	98.3±1.6	97.3±1.1	92.6±1.7	61.3±3.1	7.0±0.3
18	42.2±2.9	27.2±6.9	—	—	99.0±8.9
19	99.5±0.6	98.8±0.3	83.8±2.7	48.9±3.6	8.9±0.7
20	93.5±2.1	63.8±2.7	47.5±2.4	24.1±2.3	22.5±3.4
21	99.1±0.2	97.5±0.8	96.5±1.2	93.7±1.3	2.1±0.3
22	98.9±0.4	97.7±0.2	92.5±0.6	62.5±0.9	6.1±0.6
23	96.8±1.5	90.8±0.3	91.3±1.1	62.9±0.7	7.3±1.4
BT^a	52.6±1.5	29.8±2.3	—	—	84.1±6.5
TC^b	38.5±5.2	27.7±6.6	—	—	122.1±9.5
JHXJZ^c	97.0±0.2	96.7±0.2	96.1±0.2	54.9±1.5	7.9±0.8