Agricultural and Biological Sciences Journal
Articles Information
Agricultural and Biological Sciences Journal, Vol.6, No.1, Mar. 2020, Pub. Date: Jan. 14, 2020
Synthesis of Novel (4, 6-Dimethoxypyrimidin-2-yl) Thiosalicylate Aldoxime Esters as Herbicidal ALS Inhibitors
Pages: 1-15 Views: 94 Downloads: 49
Authors
[01] Yulin Zhou, School of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou, P. R. China.
[02] Xiangjian Xu, School of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou, P. R. China.
[03] Bin Wang, School of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou, P. R. China.
[04] Lele Zhang, School of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou, P. R. China.
[05] Hang Hu, School of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou, P. R. China.
[06] Defeng Xu, School of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou, P. R. China; National & Local Joint Engineering Research Center for High-efficiency Refining and High-quality Utilization of Biomass, Changzhou University, Changzhou, P. R. China.
Abstract
A series of new pyrimidinylthiosalicylic acid derivatives, (4, 6-dimethoxypyrimidin-2-yl) thiosalicylate aldoxime esters (6a-6x), were designed and synthesized as potential herbicidal acetolactate synthase (ALS) inhibitors. All synthesized new compounds were characterized by 1H NMR, 13C NMR, and high resolution mass spectrometry (HRMS). The herbicidal activity and in vitro ALS enzyme inhibition activity studies were performed to test the synthesized new compounds. The herbicidal activity study shows that all synthesized new compounds exhibit no herbicidal activity against Setaria viridis and Eleusine indica and no harm to rice. Among the tested compounds, 6d, 6i, 6j, 6n, 6o, and 6p exhibit potent herbicidal activity (inhibitory ratio over 85%) against barnyard grass at 10 mg/L, which are better than other synthesized new compounds and Pyriftalid. 6d, 6i, 6j, 6n, 6o, and 6p also exhibit efficient inhibitory activity (IC50 2.63-8.02 mM) against E.coli ALS enzyme in in vitro ALS enzyme inhibition activity study. The structure-activity relationship (SAR) analysis reveals that benzaldoxime ester is a highly efficient substituent group for ALS inhibitors, which is better than heteroaromatic aldoxime esters and aliphatic aldoxime ester, and the introduction of -OBoc (6n, 6o), -NH2 (6p), or -F (6d, 6i, 6j) to the benzaldoxime ester can further enhance ALS enzyme inhibition activity. Molecular docking simulation was performed to gain a better understanding of the probable binding modes of these compounds. Compounds 6d, 6i, 6j, 6n, 6o, and 6p reported in the present work may serve as new candidates for herbicidal ALS inhibitors.
Keywords
Pyrimidylsalicylates, Acetolactate Synthase Inhibitors, Aldoxime Esters, Herbicidal Activity, Molecular Docking Simulation
References
[01] Chen, C. N.; Lv, L. L.; Ji, F. Q.; Chen, Q.; Xu, H.; Niu, C. W.; Xi, Z.; Yang, G. F. (2009). Design and synthesis of N-2, 6-difluorophenyl-5-methoxyl-1, 2, 4-triazolo [1, 5-a]-pyrimidine-2-sulfonamide as acetohydroxyacid synthase inhibitor. Bioorganic & Medicinal Chemistry, 17: 3011-3017.
[02] Chen, C. N.; Chen, Q.; Liu, Y. C.; Zhu, X. L.; Niu, C. W.; Xi, Z.; Yang, G. F. (2010). Syntheses and herbicidal activity of new triazolopyrimidine-2-sulfonamides as acetohydroxyacid synthase inhibitor. Bioorganic & Medicinal Chemistry, 18: 4897-4904.
[03] Qu, R. Y.; Yang, J. F.; Devendar, P.; Kang, W. M.; Liu, Y. C.; Chen, Q.; Niu, C. W.; Xi, Z.; Yang, G. F. (2017). Discovery of New 2-[ (4, 6-Dimethoxy-1, 3, 5-triazin-2-yl) oxy]-6- (substituted phenoxy) benzoic Acids as Flexible Inhibitors of Arabidopsis thaliana Acetohydroxyacid Synthase and Its P197L Mutant. Journal of Agricultural and Food Chemistry, 65: 11170-11178.
[04] Bar-Ilan, A.; Balan, V.; Tittmann, K.; Golbik, R.; Vyazmensky, M.; Hübner, G.; Barak, Z. e.; Chipman, D. M. (2001). Binding and Activation of Thiamin Diphosphate in Acetohydroxyacid Synthase. Biochemistry, 40: 11946-11954.
[05] Ji, F. Q.; Niu, C. W.; Chen, C. N.; Chen, Q.; Yang, G. F.; Xi, Z.; Zhan, C. G. (2008). Computational design and discovery of conformationally flexible inhibitors of acetohydroxyacid synthase to overcome drug resistance associated with the W586L mutation. ChemMedChem, 3: 1203-1206.
[06] Pang, S. S.; Guddat, L. W.; Duggleby, R. G. (2003). Molecular basis of sulfonylurea herbicide inhibition of acetohydroxyacid synthase. The Journal of Biological Chemistry, 278: 7639-7644.
[07] Liu, Y. C.; Qu, R. Y.; Chen, Q.; Yang, J. F.; Cong-Wei, N.; Zhen, X.; Yang, G. F. (2016). Triazolopyrimidines as a New Herbicidal Lead for Combating Weed Resistance Associated with Acetohydroxyacid Synthase Mutation. Journal of Agricultural and Food Chemistry, 64: 4845-4857.
[08] McCourt, J. A.; Pang, S. S.; King-Scott, J.; Guddat, L. W.; Duggleby, R. G. (2006). Herbicide-binding sites revealed in the structure of plant acetohydroxyacid synthase. Proceedings of the National Academy of Sciences of the United States of America, 103: 569.
[09] Garcia, M. D.; Nouwens, A.; Lonhienne, T. G.; Guddat, L. W. (2017). Comprehensive understanding of acetohydroxyacid synthase inhibition by different herbicide families. Proceedings of the National Academy of Sciences, 114: E1091.
[10] Koo, S. J.; Kuramochi, H.; Chae, S. H. (2006). Herbicidal efficacy and selectivity of pyribenzoxim in turfgrasses. Weed Biology and Management, 6: 96-101.
[11] Chang, H.-R.; Keum, Y. S.; Koo, S.-J.; Moon, J.-K.; Kim, K.; Kim, J.-H. (2011). Metabolism of a New Herbicide, [14C] Pyribenzoxim, in Rice. Journal of Agricultural and Food Chemistry, 59: 1918-1923.
[12] Kim, B. H.; Kim, H. J.; Ok, J. H.; Kang, S. H. (2001). Analysis of a new herbicide (pyribenzoxim) residues in soil using direct-extract-injection HPLC with column switching. Journal of Liquid Chromatography & Related Technologies, 24: 669-678.
[13] Chauhan, B. S.; Johnson, D. E. (20110. Growth Response of Direct-Seeded Rice to Oxadiazon and Bispyribac-Sodium in Aerobic and Saturated Soils. Weed Science, 59: 119-122.
[14] Darren, W. L.; Stephen, E. H. (2006). Seasonal Effects on Annual Bluegrass (Poa annua) Control in Creeping Bentgrass with Bispyribac-Sodium. Weed Technology, 20: 722-727.
[15] Seo, J.-S.; Moon, J.-K.; Kim, J.-H. (2012). Photodegradation of pyribenzoxim in water. Journal of the Korean Society for Applied Biological Chemistry, 55: 391-396.
[16] Hu, Q.; Lin, G.-S.; Duan, W.-G.; Huang, M.; Lei, F.-H. (2017). Synthesis and Biological Activity of Novel (Z) - and (E) -Verbenone Oxime Esters. Molecules, 22: 1678.
[17] Chauhan, B. S.; Abeysekara, A. S. K.; Kulatunga, S. D.; Wickrama, U. B. (2013). Performance of Different Herbicides in a Dry-Seeded Rice System in Sri Lanka. Weed Technology, 27: 459-462.
[18] Schloss, J. V.; Ciskanik, L. M.; Dyk, D. E. V. (1988). Origin of the herbicide binding site of acetolactate synthase. Nature, 331: 360-362.
[19] Grundman, O.; Khozin-Goldberg, I.; Raveh, D.; Cohen, Z.; Vyazmensky, M.; Boussiba, S.; Shapira, M. (2012). Cloning, mutagenesis, and characterization of the microalga Parietochloris incisa acetohydroxyacid synthase, and its possible use as an endogenous selection marker. Biotechnology and Bioengineering, 109: 2340-2348.
[20] Meanwell, N. A. (2018). Fluorine and Fluorinated Motifs in the Design and Application of Bioisosteres for Drug Design. Journal of Medicinal Chemistry, 61: 5822-5880.
[21] Hagmann, W. K. (2008). The many roles for fluorine in medicinal chemistry. Journal of Medicinal Chemistry, 51: 4359-4369.
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