Synthesis, Herbicidal Activity and Three-Dimensional Quantitative Structure-Activity Relationship (3D-QSAR) Study of 4-Methyl- 1,2,4-triazole-thioether Compounds Containing Natural Styrene Structure

doi:10.6023/cjoc202011023

Abstract

In an attempt to search for natural renewable resource-based herbicidal agents, twenty-six novel 4-methyl-1,2,4- triazole-thioether compounds containing natural styrene structure were designed and synthesized. Their structures were confirmed by FTIR,¹H NMR, ¹³C NMR, ESI-MS and elemental analysis. The preliminary herbicidal activity test showed that, at 100 µg/mL, most of the compounds showed good inhibitory activity against the root-growth of rape ( Brassica campestris), in which 8 compounds had inhibition rate of greater than 81.4%, implying much better herbicidal activity than that of the positive control flumioxazin with inhibition rate of 63.0%. Also, 2 compounds exhibited good inhibitory activity against the seedling-growth of barnyardgrass (Echinochloa crusgalli). It was found by comparison that aliphatic R substituents or pyridine rings were beneficial to herbicidal activity. Furthermore, a preliminary three-dimensional quantitative structure-activity relationship (3D-QSAR) study was carried out by the CoMFA method for the inhibitory activity of the target compounds with aromatic R substituents against the root-growth of rape, and a reasonable and effective 3D-QSAR model (r²=0.996, q²=0.603) has been established.

Key words: styrene, cinnamaldehyde, 1,2,4-triazole-thioether, herbicidal activity, three-dimensional quantitative structure- activity relationship (3D-QSAR)

Cite this article

Chengfei Li, Bo Cen, Wengui Duan, Guishan Lin, Xiu Wang, Baoyu Li. Synthesis, Herbicidal Activity and Three-Dimensional Quantitative Structure-Activity Relationship (3D-QSAR) Study of 4-Methyl- 1,2,4-triazole-thioether Compounds Containing Natural Styrene Structure[J]. Chinese Journal of Organic Chemistry, 2021, 41(6): 2485-2495.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 9

References 45

[1]	Yang, L.; Zhou, L. Z.; Chen, H. Y.; Gu, Y. Farm. Prod. Process 2019, 2,41(in Chinese).
	( 杨漓, 周丽珠, 陈海燕, 谷瑶, 农产品加工, 2019, 2,41. )
[2]	Wu, C. H.; Shu, M.; Li, Q.; Ding, P. Chin. Med. J. Res. Prac. 2017, 31,14(in Chinese).
	( 伍彩红, 舒眉, 李倩, 丁平, 现代中药研究与实践, 2017, 31,14.)
[3]	Li, Q. Z.; Song, B. A.; Cai, X. J.; Zheng, Y. G.; Guo, Q. Q. Chin. J. Org. Chem. 2010, 30,569(in Chinese).
	( 李黔柱, 宋宝安, 蔡学建, 郑玉国, 郭晴晴, 有机化学, 2010, 30,569.)
[4]	Zhang, X. B.; Ma, H. Y.; Sun, T. D.; Lei, P.; Yang, X. L.; Zhang, X. M.; Ling, Y. Chin. J. Org. Chem. 2019, 39,2965(in Chinese). doi: 10.6023/cjoc201903031
	( 张学博, 马航宇, 孙腾达, 雷鹏, 杨新玲, 张晓鸣, 凌云, 有机化学, 2019, 39,2965.) doi: 10.6023/cjoc201903031
[5]	Marona, H.; Szkaradek, N.; Karczewska, E.; Trojanowska, D.; Budak, A.; Bober, P.; Przepiorka, W.; Marek Cegla, M.; Szneler, E. Arch. Pharm. Chem. Life Sci. 2010, 342,9. doi: 10.1002/ardp.v342:1
[6]	Xu, Y.; Lei, P.; Ling, Y.; Wang, S. W.; Yang, X. L. Chin. J. Org. Chem. 2014, 34,1118(in Chinese). doi: 10.6023/cjoc201401034
	( 徐焱, 雷鹏, 凌云, 王圣文, 杨新玲, 有机化学, 2014, 34,1118.) doi: 10.6023/cjoc201401034
[7]	Friedman, M. J. Agric. Food Chem. 2017, 65,10406. doi: 10.1021/acs.jafc.7b04344
[8]	Li, X.; sheng, J. Z.; Huang, G. H.; Ma, R. X.; Yin, F. X.; Song, D.; Zhao, C.; Ma, S. T. Eur. J. Med. Chem. 2015, 97,32. doi: 10.1016/j.ejmech.2015.04.048
[9]	Kim, H. K.; Kim, J. R.; Ahn, Y. J. J. Stored. Prod. Res. 2004, 40,55. doi: 10.1016/S0022-474X(02)00075-9
[10]	Saad, M. M. G.; Gouda, N. A. A.; Abdelgaleil, S. A. M. J. Environ. Sci. Heal. B 2019, 54,954. doi: 10.1080/03601234.2019.1653121
[11]	Chotsaeng, N.; Laosinwattana, C.; Charoenying, P. Molecules 2018, 23,471. doi: 10.3390/molecules23020471
[12]	Muñoz, M.; Torres‐Pagán, N.; Peiró, R.; Guijarro, R.; Sánchez‐Moreiras, A. M.; Verdeguer, M. Agronomy 2020, 10,791. doi: 10.3390/agronomy10060791
[13]	Zhou, J.; Yuan, X. R.; Li, L.; Zhang, T.; Wang, B. Nat. Prod. Res. 2017, 31,2909. doi: 10.1080/14786419.2017.1299724
[14]	Kwon, B. M.; Lee, S. H.; Choi, S. U.; Park, S. H.; lee, C. O.; Cho, Y. K.; Sung, N. D.; Bok, S. H. Arch. Pharm. Res. 1998, 21,147. pmid: 9875422
[15]	Ka, H.; Park, H. J.; Jung, H. J.; Choi, J. W.; Cho, K. S.; Ha, J.; Lee, K. T. Cancer Lett. 2003, 196,143. doi: 10.1016/S0304-3835(03)00238-6
[16]	Cabello, C. M.; 3rd, W. B. B.; Lamore, S. D.; Ley, S.; Bause, A. S.; Azimian, S.; Wondrak, G.T.. Free Radic. Biol. Med. 2009, 46,220. doi: 10.1016/j.freeradbiomed.2008.10.025
[17]	Wu, W. N.; Jiang, Y. M.; Zhang, B. Y.; Wang, J. Z.; Du, H. T.; Fei, Q. Chemistry 2019, 82,1115(in Chinese).
	( 吴文能, 姜阳明, 张卜艳, 王家忠, 杜海堂, 费强, 化学通报, 2019, 82,1115.)
[18]	He, S. C.; Zhang, H. Z.; Zhang, H. J.; Sun, Q.; Zhou, C. H. Med. Chem. 2020, 16,104. doi: 10.2174/1573406414666181106124852
[19]	Liu, X. H.; Sun, Z. H.; Yang, M. Y.; Tan, C. X.; Weng, J. Q.; Zhang, Y. G.; Ma, Y. Chem. Biol. Drug Des. 2014, 84,342. doi: 10.1111/cbdd.2014.84.issue-3
[20]	Rode, N. D.; Sonawane, A. D.; Nawale, L.; Khedkar, V. M.; Joshi, R. A.; Likhite, A. P.; Sarkar, D.; Joshi, R. R. Chem. Biol. Drug Des. 2017, 90,1206. doi: 10.1111/cbdd.2017.90.issue-6
[21]	Gilandoust, M.; Harsha, K. B.; Mohan, C. D.; Raquib, A. R.; Rangappa, S.; Pandey, V.; Lobie, P. E.; Basappa ; Rangappa, K. S.. Bioorg. Med. Chem. Lett. 2018, 28,2314. doi: S0960-894X(18)30420-7 pmid: 29789259
[22]	Korcz, M.; Saczewski, F.; Bednarski, P. J.; Kornicka, A. Molecules 2018, 23,1497. doi: 10.3390/molecules23061497
[23]	Massari, S.; Nannetti, G.; Desantis, J.; Muratore, G.; Sabatini, S.; Manfroni, G.; Mercorelli, B.; Cecchetti, V.; Palu, G.; Cruciani, G.; Loregian, A.; Goracci, L.; Tabarrini, O. J. Med. Chem. 2015, 58,3830. doi: 10.1021/acs.jmedchem.5b00012 pmid: 25856229
[24]	Liu, X. H.; Xu, X. Y.; Tan, C. X.; Weng, J. Q.; Xin, J. H.; Chen, J. Pest Manage. Sci. 2015, 71,292. doi: 10.1002/ps.3804
[25]	Wang, B. L.; Zhang, L. Y.; Liu, X. H.; Ma, Y.; Zhang, Y.; Li, Z. M.; Zhang, X. Bioorg. Med. Chem. Lett. 2017, 27,5457. doi: 10.1016/j.bmcl.2017.10.065
[26]	Wang, B. L.; Zhang, L. Y.; Zhan, Y. Z.; Zhang, Y.; Zhang, X.; Wang, L. Z.; Li, Z. M. J. Fluorine Chem. 2016, 184,36. doi: 10.1016/j.jfluchem.2016.02.004
[27]	Xu, W. M.; Song, B. A.; Yang, S.; Hu, D. Y.; Zeng, S. Agrochemicals 2010, 49,625(in Chinese).
	( 徐维明, 宋宝安, 杨松, 胡德禹, 曾松, 农药, 2010, 49,625.)
[28]	HRAC Classification on Mode of Action 2020. (accessed September 26, 2020). https://www.hracglobal.com.
[29]	Lu, X. L.; Zhu, X.; Zhang, M.; Wu, Q. L.; Zhou, X. D.; Li, J. K. Nat. Prod. Lett. 2019, 33,2145.
[30]	Cheng, C. R.; Zheng, Z.; Liang, R. M.; Li, F.; X. Jiang, Q. Q.; Yue, L.; Wang, Q.; Ding, J.; Liu, Y.. Chem. Nat. Compd. 2020, 56,264. doi: 10.1007/s10600-020-03003-4
[31]	Chen, Y.; Li, P.; Chen, M.; He, J.; Su, S. J.; He, M.; Wang, H.; Xue, W. J. Heterocycl. Chem. 2020, 57,1. doi: 10.1002/jhet.v57.1
[32]	Ruan, X. H.; Zhang, C.; Jiang, S. C.; Guo, T.; Xia, R. J.; Chen, Y.; Tang, X.; Xue, W. Molecules 2018, 23,3132. doi: 10.3390/molecules23123132
[33]	Barrows, R. D.; Hammill, J. T.; Michael, C. Tran, M. C.; Falade, M. O.; Rice, A. L.; Davis, C. W.; Emge, T. J.; Rablen, P. R.; Guy, R. K.; Knapp, S. Bioorg. Med. Chem. 2020 , 28, 115758..
[34]	Guo, Y.; Wang, X. G.; Fan, J. P.; Zhang, Q.; Wang, Y.; Zhao, Y.; Huang, M. X.; Ding, M.; Zhang, Y. B. Roy. Soc. Open Sci. 2017, 4,171053.
[35]	Yu, Y. P.; Duan, W. G.; Lin, G. S.; Kang, G. Q.; Wang, X. Y.; Lei, F. H. Chin. J. Org. Chem. 2020, 40,1647(in Chinese). doi: 10.6023/cjoc201912042
	( 虞友培, 段文贵, 林桂汕, 康国强, 王晓宇, 雷福厚, 有机化学, 2020, 40,1647.) doi: 10.6023/cjoc201912042
[36]	Li, F. Y.; Huang, L.; Zhou, X. Q.; Li, Q.; Ma, X. L.; Duan, W. G.; Wang, X. Chin. J. Org. Chem. 2020, 40,2845(in Chinese). doi: 10.6023/cjoc202003062
	( 李芳耀, 黄琳, 周小群, 李倩, 马献力, 段文贵, 王秀, 有机化学, 2020, 40,2845.) doi: 10.6023/cjoc202003062
[37]	Lin, G. S.; Chen, Z. C.; Duan, W. G.; Wang, X. Y.; Lei, F. H. Chin. J. Org. Chem. 2018, 38,2085(in Chinese). doi: 10.6023/cjoc201801043
	( 林桂汕, 陈智聪, 段文贵, 王晓宇, 雷福厚, 有机化学, 2018, 38,2085.) doi: 10.6023/cjoc201801043
[38]	He, Y.; Duan, W. G.; Lin, G. S.; Cen, B.; Bu, J. W.; Lei, F. H. Chem. Ind. Forest Prod. 2020, 40,76(in Chinese).
	( 何云, 段文贵, 林桂汕, 岑波, 卜俊文, 雷福厚, 林产化学与工业, 2020, 40,76.)
[39]	Lin, G. S.; Bai, X.; Duan, W. G.; Cen, B.; Huang, M.; Lu, S. Z. ACS Sustainable Chem. Eng. 2019, 7,7862. doi: 10.1021/acssuschemeng.9b00254
[40]	Lin, G. S.; Duan, W. G.; Yang, L. X.; Huang, M.; Lei, F. H. Molecules 2017, 22,193. doi: 10.3390/molecules22020193
[41]	Verma, J.; Khedkar, V. M.; Coutinho, E. C. Curr. Top. Med. Chem. 2010, 10,95. doi: 10.2174/156802610790232260
[42]	Li, L. H.; Li, Z. R.; Liu, M. L.; Shen, W. Y.; Wang, B.; Guo, H. Y.; Lu, Y. Molecules 2015, 21,49. doi: 10.3390/molecules21010049
[43]	Liu, M.X; Li, C. J.. Angew. Chem. Int. Ed. 2016, 55,10806. doi: 10.1002/anie.201604847
[44]	Li, L. H.; Li, Z. R.; Liu, M. L.; Shen, W. Y.; Wang, B.; Guo, H. Y.; Lu, Y. Molecules 2016, 21,49. doi: 10.3390/molecules21010049
[45]	Su, N. N.; Li, Y.; Yu, S. J.; Zhang, X.; Liu, X. H.; Zhao, W. G. Res. Chem. Intermediat. 2012, 39,759. doi: 10.1007/s11164-012-0595-9

Compd.	B. campestris		E. crusgalli
Compd.	10 μg/mL	100 μg/mL	10 μg/mL	100 μg/mL
Flumioxazin	57.8	63.0	95.1	97.5
5a	30.7	74.9	5.0	20.0
5b	68.9	86.9	15.0	40.0
5c	79.3	89.4	25.0	40.0
5d	41.7	90.5	0	0
5e	67.5	83.2	0	0
5f	38.3	76.8	0	0
5g	22.6	75.7	10.0	40.0
5h	25.3	77.4	35.0	70.0
5i	38.9	81.4	15.0	75.0
5j	10.0	47.9	20.0	50.0
5k	0	79.3	20.0	40.0
5l	34.0	73.0	35.0	55.0
5m	13.8	65.1	15.0	30.0
5n	4.6	31.8	10.0	25.0
5o	25.8	60.5	10.0	25.0
5p	4.6	18.7	0	0
5q	20.9	81.7	15.0	20.0
5r	29.6	52.3	20.0	50.0
5s	0	9.0	0	10.0
5t	23.7	57.8	0	0
5u	21.1	25.2	0	10.0
5v	37.2	79.1	0	0
5w	24.5	55.1	0	10.0
5x	60.7	83.2	0	10.0
5y	45.0	60.2	0	0
5z	30.8	85.6	0	0

Compd.	B. campestris		E. crusgalli
Compd.	10 μg/mL	100 μg/mL	10 μg/mL	100 μg/mL
Flumioxazin	57.8	63.0	95.1	97.5
5a	30.7	74.9	5.0	20.0
5b	68.9	86.9	15.0	40.0
5c	79.3	89.4	25.0	40.0
5d	41.7	90.5	0	0
5e	67.5	83.2	0	0
5f	38.3	76.8	0	0
5g	22.6	75.7	10.0	40.0
5h	25.3	77.4	35.0	70.0
5i	38.9	81.4	15.0	75.0
5j	10.0	47.9	20.0	50.0
5k	0	79.3	20.0	40.0
5l	34.0	73.0	35.0	55.0
5m	13.8	65.1	15.0	30.0
5n	4.6	31.8	10.0	25.0
5o	25.8	60.5	10.0	25.0
5p	4.6	18.7	0	0
5q	20.9	81.7	15.0	20.0
5r	29.6	52.3	20.0	50.0
5s	0	9.0	0	10.0
5t	23.7	57.8	0	0
5u	21.1	25.2	0	10.0
5v	37.2	79.1	0	0
5w	24.5	55.1	0	10.0
5x	60.7	83.2	0	10.0
5y	45.0	60.2	0	0
5z	30.8	85.6	0	0

q²	r²	S	N	F	Contribution/%
q²	r²	S	N	F	Steric	Electrostatic
0.603	0.996	0.040	6	337.11	36.2	63.8

q²	r²	S	N	F	Contribution/%
q²	r²	S	N	F	Steric	Electrostatic
0.603	0.996	0.040	6	337.11	36.2	63.8

Compd.	ED	ED''	Residue
5f	–1.97	–2.03	0.06
5g	–2.01	–2.00	–0.01
5h	–1.97	–1.97	0
5i	–1.89	–1.90	0.01
5j	–2.56	–2.56	0
5k	–1.93	–1.90	–0.03
5l	–2.08	–2.03	–0.05
5m	–2.24	–2.23	–0.01
5n	–2.86	–2.84	–0.02
5o	–2.35	–2.32	–0.03
5s	–3.55	–3.55	0
5t	–2.47	–2.45	–0.02
5u	–3.03	–3.05	0.02
5v	–1.96	–2.01	0.05
5w	–2.49	–2.52	0.03
5p*	–3.17	–3.06	–0.11
5q*	–1.94	–1.98	0.04
5r*	–2.55	–2.64	0.09

含天然苯乙烯结构的4-甲基-1,2,4-三唑-硫醚化合物的合成、除草活性及三维定量构效关系(3D-QSAR)研究