Design, Synthesis and Antifungal Bioactivity Evaluation of Thiazole Benzoate Derivatives

doi:10.6023/cjoc202206030

Abstract

Plant pathogenic fungi seriously threaten agricultural production, and there is an urgent need to develop new high efficiency and low toxicity fungicides. In this article, a series of new thiazole benzoate derivatives are designed and synthesized. The preliminary screening results showed that 1-(4,5-dimethylthiazol-2-yl)-2-methylpropyl benzoate (3), (3- chlorophenyl)(4,5-dimethylthiazol-2-yl)methyl benzoate (5), and (4,5-dimethylthiazol-2-yl)(m-tolyl)methyl benzoate (8) showed good inhibitory activities against Botrytis cinerea and Sclerotinia sclerotiorum. Among them, compound 8 has the best inhibitory activity against Botrytis cinerea and Sclerotinia sclerotiorum with EC₅₀ values of 13.82 and 3.66 mg/L, respectively. Preliminary physiological and biochemical experiments showed that compound 8 caused certain damage to Sclerotinia sclerotiorum cell membrane.

Key words: benzoicacid, thiazole, antifungal activity, Sclerotinia sclerotiorum, Botrytis cinerea

Cite this article

Meng Li, Dongguo Xia, Yunxiao Wang, Xiang Cheng, Jiexiu Gong, Yao Chen, Xianhai Lü. Design, Synthesis and Antifungal Bioactivity Evaluation of Thiazole Benzoate Derivatives[J]. Chinese Journal of Organic Chemistry, 2023, 43(2): 686-696.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 10

References 30

[1]	Bolton, M. D.; Thomma, B. P. H. J.; Nelson, B. D. Mol. Plant. Pathol. 2006, 7. 1.
[2]	Huang, X.-P.; Song, Y.-F.; Li, B.-X.; Mu, W.; Liu, F. Crop Prot. 2019, 122, 42. doi: 10.1016/j.cropro.2019.04.010
[3]	Zhu, J.-K.; Gao, J-M.; Yang, C.-J.; Shang, X.-F.; Zhao, Z.-M.; Lawoe, R.-K.; Zhou, R.; Sun, Y.; Yin, X.-D.; Liu, Y. Q. J. Agric. Food Chem. 2020, 68, 2306. doi: 10.1021/acs.jafc.9b06793
[4]	Cheng, X.; Wang, W.; Wang, Y.-X.; Xia, D.-G.; Yin, F.; Liu, Q.; Luo, H.; Li, M.; Zhang, C.-Q.; Cao, H.-Q.; Lv, X.-H. J. Agric. Food Chem. 2021, 69, 11395. doi: 10.1021/acs.jafc.1c02454
[5]	Yao, T.-T.; Fang, S.-W.; Li, Z.-S.; Xiao, D.-X.; Cheng, J.-L.; Ying, H.-Z.; Du, Y.-J.; Zhao, J.-H.; Dong, X.-W. J. Agric. Food Chem. 2017, 65, 3204. doi: 10.1021/acs.jafc.7b00249
[6]	Wang, W.; Zhang, S.; Wang, J.-H.; Wu, F.-R.; Wang, T.; Xu, G. J. Agric. Food Chem. 2021, 69, 491. doi: 10.1021/acs.jafc.0c06700
[7]	Wang, X.; Wang, A.; Qiu, L.; Chen, M.; Lu, A.; Li, G.; Yang, C.; Xue, W. J. Agric. Food Chem. 2020, 68, 14426. doi: 10.1021/acs.jafc.0c03736
[8]	Wu, Z.; Park, H.-Y.; Xie, D.; Yang, J.; Hou, S.; Shahzad, N.; Kim, C. K.; Yang, S. J. Agric. Food Chem. 2021, 69, 1214. doi: 10.1021/acs.jafc.0c05702
[9]	Guo, X.; Zhao, B.; Fan, Z.; Yang, D.-Y.; Belskaya, N. P. J. Agric. Food Chem. 2019, 67, 1647. doi: 10.1021/acs.jafc.8b06935
[10]	Chen, L.; Zhao, Bin.; Fan, Z.-J.; Hu, M.-X.; Li, Q.; Hu, W.-H.; Li, J.-W.; Zhang, J.-L. J. Agric. Food Chem. 2019, 67, 12357. doi: 10.1021/acs.jafc.9b03891
[11]	Lu, Q.; Yu, Q.; Zhu, Y.-B.; Weng, J.-Q.; Yuan, J.; Hu, D.-X.; Chen, J.; Liu, X.-H.; Tan, C.-X. J. Mol. Struct. 2019, 1180, 780. doi: 10.1016/j.molstruc.2018.12.068
[12]	Wu, Q.; Zhao, B.; Fan, Z.-J.; Guo, X.-F.; Yang, D.-Y.; Zang, N.-L.; Yu, B.; Zhou, S.; Zhao, J.-B.; Chen, F. J. Agric. Food Chem. 2019, 67, 1360. doi: 10.1021/acs.jafc.8b06054
[13]	Yu, B.; Zhou, S.; Cao, L.-X.; Hao, Z.-S.; Yang, D.-Y.; Guo, X.-F.; Zhang, N.-L.; Bakulev, V.A.; Fan, Z.-J. J. Agric. Food Chem. 2020, 68, 7093. doi: 10.1021/acs.jafc.0c00062
[14]	Jr, H; Phares, H.F. Otto, E.J.J.o.I.D. J. Invest. Dermatol. 1964, 42, 479. doi: 10.1038/jid.1964.101
[15]	Yang, Y.; Dong, F.-S.; Liu, X.-G.; Xu, J.; Wu, X.-H.; Zheng, Y.-Q. Environ. Pollut. 2020, 265, 115031. doi: 10.1016/j.envpol.2020.115031
[16]	Kim, D. S.; Chun, S. J.; Jeon, J. J.; Lee, S. W.; Joe, G. H. Pest. Manage. Sci. 2004, 60, 1007. doi: 10.1002/ps.873
[17]	Cohen, Y. J.; Rubin, A. E.; Galperin, M. Phytoparasitica 2018, 46, 689. doi: 10.1007/s12600-018-0702-6
[18]	Gao, Y.-Y.; Zhao, X.-J.; Sun, X.-F.; Wang, Z.; Zhang, J.; Li, L.-S.; Shi, H.-Y.; Wang, M.-H. J. Agric. Food Chem. 2021, 69, 3289. doi: 10.1021/acs.jafc.0c04163
[19]	Siegenthaler, T. B.; Hansen, Z. Plant Dis. 2021, 105, 1943.
[20]	Guo, Y.; Fan, J.-P.; Zhang, Q.; Bao, C.-N.; Liu, Z.-Y.; Yang, R. G. Bioorg. Med. Chem. Lett. 2019, 29, 179. doi: 10.1016/j.bmcl.2018.12.002
[21]	Soliman, N. N.; Salam, M. A. E.; Fadda, A. A.; Abdel-Motaal, M. J. Agric. Food Chem. 2020, 68,5790.
[22]	Liu, H.; Xia, D.-G.; Chu, Z.-W.; Hu, R.; Lv, X.-H. Bioorg. Chem. 2020, 100, 103907. doi: 10.1016/j.bioorg.2020.103907
[23]	Mattson, A. E.; Bharadwaj, A. R.; Zuhl, A. M.; Scheidt, K. A. J. Org. Chem. 2006, 71. 5715.
[24]	Mattson, A. E.; Zuhl, A. M.; Reynolds, T. E.; Scheidt, K. A. J. Am. Chem. Soc. 2006, 128, 4932. pmid: 16608309
[25]	Ren, Z.-L.; Liu, H.; Jiao, D.; Hu, H.-T.; Wang, Wei.; Gong, J.-X.; Wang, A.-L.; Cao, H.-Q.; Lv, X.-H. Drug Dev. Res. 2018, 79, 307. doi: 10.1002/ddr.21469
[26]	Liu, H.; Xia, D.-G.; Hu, R.; Wang, W.; Cheng, X.; Wang, A.-L.; Zhang, Q.; Lv, X.-H. Pestic. Biochem. Phys. 2020, 163, 271. doi: 10.1016/j.pestbp.2019.11.024
[27]	Wang, W.; Cheng, X.; Cui, X.; Xia, D.-G.; Wang, Z.-Q.; Lv, X.-H. Pest. Manage. Sci. 2021, 77, 3529. doi: 10.1002/ps.6406
[28]	Yin, X.-D.; Ma, K.-Y.; Wang, Y.-L.; Sun, Y.; Shang, X.-F.; Zhao, Z.-M.; Wang, R.-X; Chen, Y.-J.; Zhu, J.-K.; Liu, Y.-Q. J. Agric. Food Chem. 2020, 68, 11096. doi: 10.1021/acs.jafc.0c01322
[29]	Magdalena, E.-S.; Agnieszka, N.; Agata, C.; Monika, Ś.; Anna, O.; Dorota, Ż. Food Chem. 2021, 350, 129218. doi: 10.1016/j.foodchem.2021.129218
[30]	Sabatino, V.; Rebelein, J. G.; Ward, T. R. J. Am. Chem. Soc. 2019, 141, 17048. doi: 10.1021/jacs.9b07193 pmid: 31503474

Compd.	R¹	R²		Inhibition rate^a/%
Compd.	R¹	R²		B. cinerea^b	V. mali^c	S. sclerotiorum^d
1	Phenyl	H		15.4±0.7	25.8±1.2	30.2±1.3
2	1-Naphthyl	H		45.6±0.9	16.9±1.4	10.5±1.8
3	Isopropyl	H		72.3±1.5	72.6±0.9	83.2±1.1
4	2-Cl-Phenyl	H		22.6±1.5	41.3±0.8	20.1±0.8
5	3-Cl-Phenyl	H		77.4±2.2	38.7±1.6	56.0±1.4
6	4-Cl-Phenyl	H		32.3±1.1	12.9±0.7	26.3±2.9
7	2-CH₃-Phenyl	H		13.1±2.4	21.6±1.2	43.5±0.9
8	3-CH₃-Phenyl	H		95.3±3.5	61.2±1.8	94.9±1.6
9	4-CH₃-Phenyl	H		23.0±1.5	31.5±1.4	18.4±0.7
10	Isopropyl	2-Cl		30.5±0.9	61.5±0.3	20.1±0.3
11	Isopropyl	3-Cl		86.9±2.0	53.4±2.5	90.9±1.1
12	Isopropyl	4-Cl		83.3±1.3	41.9±2.2	85.2±0.3
13	Isopropyl	2-CH₃		16.4±0.5	63.3±1.0	67.6±1.4
14	Isopropyl	3-CH₃		90.6±0.7	81.6±2.4	88.2±2.1
15	Isopropyl	4-CH₃		44.3±1.9	65.3±2.0	65.2±1.6
16	Isopropyl	2-CF₃		19.1±0.6	61.2±1.3	63.8±0.3
17	Isopropyl	3-CF₃		48.3±1.3	61.6±0.5	33.6±0.6
18	Isopropyl	4-CF₃		30.6±1.7	57.5±1.1	65.0±1.2
19	3-Cl-Phenyl	2-Cl		82.2±0.6	55.1±1.9	56.0±1.8
20	3-Cl-Phenyl	3-Cl		11.5±0.5	30.6±0.7	5.1±1.2
21	3-Cl-phenyl	4-Cl		82.9±2.0	51.0±1.5	85.3±0.9
22	3-Cl-Phenyl	2-CH₃		88.2±1.5	12.3±0.3	95.1±1.4
23	3-Cl-Phenyl	3-CH₃		16.4±1.9	9.8±1.3	61.6±0.4
24	3-Cl-Phenyl	4-CH₃		40.1±0.8	8.2±1.4	81.6±0.2
25	3-Cl-Phenyl	2-CF₃		45.3±9.5	14.5±0.2	56.2±1.3
26	3-Cl-Phenyl	3-CF₃		35.8±1.2	16.2±0.6	40.8±1.8
27	3-Cl-Phenyl	4-CF₃		21.5±0.4	65.1±2.2	30.8±1.6
28	3-CH₃-Phenyl	2-Cl		84.4±0.6	55.6±1.2	26.4±1.3
30	3-CH₃-Phenyl	4-Cl		60.9±1.2	36.9±0.5	40.6±0.7
31	3-CH₃-Phenyl	2-CH₃		57.3±2.0	45.4±1.3	35.1±0.3
32	3-CH₃-Phenyl	3-CH₃		56.7±0.7	26.4±0.5	16.7±1.4
Compd.	R¹	R²	Inhibition rate^a/%
Compd.	R¹	R²	B. cinerea^b		V. mali^c	S. sclerotiorum^d
33	3-CH₃-Phenyl	4-CH₃	44.3±0.5		61.0±2.2	19.2±2.1
34	3-CH₃-Phenyl	2-CF₃	58.0±1.5		20.3±0.4	15.6±1.5
35	3-CH₃-Phenyl	3-CF₃	65.4±1.9		9.1±1.5	6.4±0.5
36	3-CH₃-Phenyl	4-CF₃	45.6±1.3		30.7±1.1	46.5±1.8
Boscalid	-	-	100.0		95.3	100.0

Compd.	R¹	R²		Inhibition rate^a/%
Compd.	R¹	R²		B. cinerea^b	V. mali^c	S. sclerotiorum^d
1	Phenyl	H		15.4±0.7	25.8±1.2	30.2±1.3
2	1-Naphthyl	H		45.6±0.9	16.9±1.4	10.5±1.8
3	Isopropyl	H		72.3±1.5	72.6±0.9	83.2±1.1
4	2-Cl-Phenyl	H		22.6±1.5	41.3±0.8	20.1±0.8
5	3-Cl-Phenyl	H		77.4±2.2	38.7±1.6	56.0±1.4
6	4-Cl-Phenyl	H		32.3±1.1	12.9±0.7	26.3±2.9
7	2-CH₃-Phenyl	H		13.1±2.4	21.6±1.2	43.5±0.9
8	3-CH₃-Phenyl	H		95.3±3.5	61.2±1.8	94.9±1.6
9	4-CH₃-Phenyl	H		23.0±1.5	31.5±1.4	18.4±0.7
10	Isopropyl	2-Cl		30.5±0.9	61.5±0.3	20.1±0.3
11	Isopropyl	3-Cl		86.9±2.0	53.4±2.5	90.9±1.1
12	Isopropyl	4-Cl		83.3±1.3	41.9±2.2	85.2±0.3
13	Isopropyl	2-CH₃		16.4±0.5	63.3±1.0	67.6±1.4
14	Isopropyl	3-CH₃		90.6±0.7	81.6±2.4	88.2±2.1
15	Isopropyl	4-CH₃		44.3±1.9	65.3±2.0	65.2±1.6
16	Isopropyl	2-CF₃		19.1±0.6	61.2±1.3	63.8±0.3
17	Isopropyl	3-CF₃		48.3±1.3	61.6±0.5	33.6±0.6
18	Isopropyl	4-CF₃		30.6±1.7	57.5±1.1	65.0±1.2
19	3-Cl-Phenyl	2-Cl		82.2±0.6	55.1±1.9	56.0±1.8
20	3-Cl-Phenyl	3-Cl		11.5±0.5	30.6±0.7	5.1±1.2
21	3-Cl-phenyl	4-Cl		82.9±2.0	51.0±1.5	85.3±0.9
22	3-Cl-Phenyl	2-CH₃		88.2±1.5	12.3±0.3	95.1±1.4
23	3-Cl-Phenyl	3-CH₃		16.4±1.9	9.8±1.3	61.6±0.4
24	3-Cl-Phenyl	4-CH₃		40.1±0.8	8.2±1.4	81.6±0.2
25	3-Cl-Phenyl	2-CF₃		45.3±9.5	14.5±0.2	56.2±1.3
26	3-Cl-Phenyl	3-CF₃		35.8±1.2	16.2±0.6	40.8±1.8
27	3-Cl-Phenyl	4-CF₃		21.5±0.4	65.1±2.2	30.8±1.6
28	3-CH₃-Phenyl	2-Cl		84.4±0.6	55.6±1.2	26.4±1.3
30	3-CH₃-Phenyl	4-Cl		60.9±1.2	36.9±0.5	40.6±0.7
31	3-CH₃-Phenyl	2-CH₃		57.3±2.0	45.4±1.3	35.1±0.3
32	3-CH₃-Phenyl	3-CH₃		56.7±0.7	26.4±0.5	16.7±1.4
Compd.	R¹	R²	Inhibition rate^a/%
Compd.	R¹	R²	B. cinerea^b		V. mali^c	S. sclerotiorum^d
33	3-CH₃-Phenyl	4-CH₃	44.3±0.5		61.0±2.2	19.2±2.1
34	3-CH₃-Phenyl	2-CF₃	58.0±1.5		20.3±0.4	15.6±1.5
35	3-CH₃-Phenyl	3-CF₃	65.4±1.9		9.1±1.5	6.4±0.5
36	3-CH₃-Phenyl	4-CF₃	45.6±1.3		30.7±1.1	46.5±1.8
Boscalid	-	-	100.0		95.3	100.0

Fungi	Compd.	EC₅₀/(mg•L^-1)	95% confidence interval	Regression equation^a	R^b
B. cinerea	3	32.61	29.13~36.99	y=5.581x-8.446	0.998
	5	31.60	28.24~35.81	y=5.550x-8.323	0.988
	8	13.82	12.27~15.58	y=4.690x-5.349	0.989
	11	21.17	18.97~23.72	y=5.422x-7.188	0.989
	12	21.81	14.06~40.87	y=3.120x-4.176	0.942
	14	15.31	13.56~17.32	y=4.513x-5.347	0.994
	19	21.85	19.01~25.43	y=3.941x-5.010	0.986
	21	23.36	15.85~40.05	y=3.498x-4.787	0.962
	22	19.25	17.11~21.77	y=4.765x-6.120	0.995
	28	23.17	20.27~26.85	y=3.974x-5.420	0.980
	Boscalid	0.88	0.03~1.77	y=2.340x＋0.134	0.971
V. mali	3	30.74	27.42~34.90	y=5.375x-7.996	0.999
	14	15.90	13.82~18.40	y=3.576x-4.296	0.980
	Boscalid	13.44	11.55~16.13	y=3.804x-4.292	0.978
S. sclerotiorum	3	12.07	10.22~14.20	y=2.919x-3.156	0.988
	8	3.66	2.57~4.70	y=2.370x-1.335	0.986
	11	8.79	7.28~10.46	y=2.689x-2.538	0.988
	12	15.74	13.76~18.08	y=3.830x-4.584	0.986
	14	12.38	10.80~14.20	y=3.755x-4.104	0.986
	21	22.90	20.41~25.89	y=5.008x-6.810	0.993
	22	13.81	9.92~19.38	y=5.166x-5.891	0.983
	24	16.59	14.38~19.27	y=3.492x-4.260	0.985
	Boscalid	0.95	0.53~1.35	y=2.052x＋0.049	0.960

Fungi	Compd.	EC₅₀/(mg•L^-1)	95% confidence interval	Regression equation^a	R^b
B. cinerea	3	32.61	29.13~36.99	y=5.581x-8.446	0.998
	5	31.60	28.24~35.81	y=5.550x-8.323	0.988
	8	13.82	12.27~15.58	y=4.690x-5.349	0.989
	11	21.17	18.97~23.72	y=5.422x-7.188	0.989
	12	21.81	14.06~40.87	y=3.120x-4.176	0.942
	14	15.31	13.56~17.32	y=4.513x-5.347	0.994
	19	21.85	19.01~25.43	y=3.941x-5.010	0.986
	21	23.36	15.85~40.05	y=3.498x-4.787	0.962
	22	19.25	17.11~21.77	y=4.765x-6.120	0.995
	28	23.17	20.27~26.85	y=3.974x-5.420	0.980
	Boscalid	0.88	0.03~1.77	y=2.340x＋0.134	0.971
V. mali	3	30.74	27.42~34.90	y=5.375x-7.996	0.999
	14	15.90	13.82~18.40	y=3.576x-4.296	0.980
	Boscalid	13.44	11.55~16.13	y=3.804x-4.292	0.978
S. sclerotiorum	3	12.07	10.22~14.20	y=2.919x-3.156	0.988
	8	3.66	2.57~4.70	y=2.370x-1.335	0.986
	11	8.79	7.28~10.46	y=2.689x-2.538	0.988
	12	15.74	13.76~18.08	y=3.830x-4.584	0.986
	14	12.38	10.80~14.20	y=3.755x-4.104	0.986
	21	22.90	20.41~25.89	y=5.008x-6.810	0.993
	22	13.81	9.92~19.38	y=5.166x-5.891	0.983
	24	16.59	14.38~19.27	y=3.492x-4.260	0.985
	Boscalid	0.95	0.53~1.35	y=2.052x＋0.049	0.960

苯甲酸噻唑酯类衍生物的设计、合成及抗真菌活性评价