Design, Synthesis and Antibacterial Activity of 1,3,4-Oxadiazole Sufones Containing Sulfonamide Structure

doi:10.6023/cjoc202204068

Abstract

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

Cite this article

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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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

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