1,2,4-Oxadiazole-Based Bio-Isosteres of Benzamides: Synthesis, Biological Activity and Toxicity to Zebrafish Embryo
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis of Target Compounds
2.2. Spectrum Analysis of Target Compounds
2.3. Biological Activities of Target Compounds
2.4. Toxicity to Zebrafish Embryo
3. Experimental Section
3.1. General Information
3.2. Synthesis
3.2.1. Synthesis of Intermediate Ⅰ
3.2.2. Synthesis of Intermediate Ⅱ
3.2.3. Methyl 2-Chloro-5-(5-(6-Chloro-3-(Ethylthio) Pyridin-2-yl)-1,2,4-Oxadiazol-3-yl) Benzoate (7)
3.2.4. 2-Chloro-5-(5-(6-Chloro-3-(Ethylthio) Pyridin-2-yl)-1,2,4-Oxadiazol-3-yl) Benzoic Acid (8)
3.2.5. Synthesis of Target Compound 9
3.2.6. Synthesis of Target Compound 10
3.3. Biological Activity and Toxicity Determination
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
- Verger, P.J.P.; Boobis, A.R. Reevaluate pesticides for food security and safety. Science 2013, 341, 717–718. [Google Scholar] [CrossRef]
- Wang, B.L.; Zhu, H.W.; Ma, Y.; Xiong, L.X.; Li, Y.Q.; Zhao, Y.; Zhang, J.F.; Chen, Y.W.; Zhou, S.; Li, Z.M. Synthesis, insecticidal activities, and SAR studies of novel pyridylpyrazole acid derivatives based on amide bridge modification of anthranilic diamide insecticides. J. Agric. Food Chem. 2013, 61, 5483–5493. [Google Scholar] [CrossRef] [PubMed]
- Oerke, E.C. Crop losses to pests. J. Agric. Sci. 2006, 144, 31–43. [Google Scholar] [CrossRef]
- Shi:, J.J.; Ren, G.H.; Wu, N.-J.; Weng, J.-Q.; Xu, T.-M.; Liu, X.-H.; Tan, C.-X. Design, synthesis and insecticidal activities of novel anthranilic diamides containing polyfluoroalkyl pyrazole moiety. Chin. Chem. Lett. 2017, 28, 1727–1730. [Google Scholar] [CrossRef]
- Alnufaie, R.; Alsup, N.; Whitt, J.; Chambers, A.S.; Gilmore, D.; Alam, M.A. Synthesis and Antimicrobial Studies of Coumarin-Substituted Pyrazole Derivatives as Potent Anti-Staphylococcus aureus Agents. Molecules 2020, 25, 2758. [Google Scholar] [CrossRef] [PubMed]
- Avenot, H.F.; Michailides, T.J. Progress in understanding molecular mechanisms and evolution of resistance to succinate dehydrogenase inhibiting (SDHI) fungicides in phytopathogenic fungi. Crop Prot. 2010, 29, 643–651. [Google Scholar] [CrossRef]
- Fuentes-Gutiérrez, A.; Curiel-Quesada, E.; Correa-Basurto, J.; Martínez-Muñoz, A.; Reyes-Arellano, A. N-Heterocycles Scaffolds as Quorum Sensing Inhibitors. Design, Synthesis, Biological and Docking Studies. Int. J. Mol. Sci. 2020, 21, 9512. [Google Scholar]
- Hu, Y.; Li, C.Y.; Wang, X.M.; Yang, Y.H.; Zhu, H.L. 1,3,4-Thiadiazole: Synthesis, reactions, and applications in medicinal, agricultural, and materials chemistry. Chem. Rev. 2014, 114, 5572–5610. [Google Scholar] [CrossRef] [PubMed]
- Guo, X.; Zhao, B.; Fan, Z.J.; Yang, D.Y.; Zhang, N.L.; Wu, Q.F.; Yu, B.; Zhou, S.; Kalinina, T.A.; Belskaya, N.P. Discovery of novel thiazole carboxamides as antifungal succinate dehydrogenase inhibitors. J. Agric. Food Chem. 2019, 67, 1647–1655. [Google Scholar] [CrossRef]
- Duchowicz, P.R.; Vitale, M.G.; Castro, E.A.; Fernández, M.; Caballero, J. QSAR analysis for heterocyclic antifungals. Bioorg. Med. Chem. 2007, 15, 2680–2689. [Google Scholar] [CrossRef]
- Du, S.J.; Lu, H.Z.; Yang, D.Y.; Li, H.; Gu, X.L.; Wan, C.; Jia, C.M.; Wang, M.; Li, X.Y.; Qin, Z.H. Synthesis, antifungal activity and QSAR of some novel carboxylic acid amides. Molecules 2015, 20, 4071–4087. [Google Scholar] [CrossRef] [Green Version]
- Hou, Y.P.; Mao, X.W.; Wang, J.X.; Zhan, S.W.; Zhou, M.G. Sensitivity of Fusarium asiaticum to a novel succinate dehydrogenase inhibitor fungicide pydiflumetofen. Crop Prot. 2017, 96, 237–244. [Google Scholar] [CrossRef] [Green Version]
- Liu, X.H.; Qiao, L.; Zhai, Z.W.; Cai, P.P.; Cantrell, C.L.; Tan, C.X.; Weng, J.Q.; Han, L.; Wu, H.K. Novel 4-Pyrazole Carboxamide Derivatives Containing Flexible Chain Motif: Design, Synthesis and Antifungal Activity. Pest Manag. Sci. 2019, 75, 2892–2900. [Google Scholar] [CrossRef]
- Wu, Y.Y.; Shao, W.B.; Zhu, J.J.; Long, Z.Q.; Liu, L.W.; Wang, P.Y.; Li, Z.; Yang, S. Novel 1, 3, 4-Oxadiazole-2-carbohydrazides as Prospective Agricultural Antifungal Agents Potentially Targeting Succinate Dehydrogenase. J. Agric. Food Chem. 2019, 67, 13892–13903. [Google Scholar] [CrossRef]
- Hua, X.W.; Liu, W.R.; Su, Y.Y.; Liu, X.H.; Liu, J.B.; Liu, N.N.; Wang, G.Q.; Jiao, X.Q.; Fan, X.Y.; Xue, C.M.; et al. Studies on the novel pyridine sulfide containing SDH based heterocyclic amide fungicide. Pest Manag. Sci. 2020, 76, 2368–2378. [Google Scholar] [CrossRef]
- Eckroat, T.J.; Manross, D.L.; Cowan, S.C. Merged Tacrine-Based, Multitarget-Directed Acetylcholinesterase Inhibitors 2015-Present: Synthesis and Biological Activity. Int. J. Mol. Sci. 2020, 21, 5696. [Google Scholar] [CrossRef]
- Zhang, A.G.; Zhou, J.Y.; Tao, K.; Hou, T.P.; Jin, H. Design, synthesis and antifungal evaluation of novel pyrazole carboxamides with diarylamines scaffold as potent succinate dehydrogenase inhibitors. Bioorg. Med. Chem. Lett. 2018, 28, 3042–3045. [Google Scholar] [CrossRef] [PubMed]
- Wang, L.; Dai, F.Y.; Zhu, J.; Dong, K.K.; Wang, Y.L.; Chen, T. Synthesis and antibacterial activities of pleuromutilin derivatives with thiazole-5-carboxamide and thioether moiety. J. Chem. Res. 2011, 35, 313–316. [Google Scholar] [CrossRef]
- Fu, Q.; Cai, P.P.; Cheng, L.; Zhong, L.K.; Shen, Z.H.; Han, L.; Liu, X.H. Synthesis and herbicidal activity of novel pyrazole aromatic ketone analogs as HPPD inhibitor. Pest Manag. Sci. 2020, 76, 868–879. [Google Scholar] [CrossRef] [PubMed]
- Liu, X.H.; Yu, W.; Min, L.J.; Wedge, D.E.; Weng, J.Q.; Wu, H.-K.; Cantrell, C.L.; Bajsa-Hirschel, J.; Hua, X.-W. Synthesis and pesticidal activities of quinoxalines. J. Agric. Food Chem. 2020, 68, 7324–7332. [Google Scholar] [CrossRef]
- Cheng, L.; Zhang, R.R.; Wu, H.K.; Xu, T.M.; Liu, X.H. The synthesis of 6-(tertbutyl)-8-fluoro-2,3-dimethylquinoline carbonate derivatives and their antifungal activity against Pyricularia oryzae. Front. Chem. Sci. Eng. 2019, 13, 369–376. [Google Scholar] [CrossRef]
- Yao, T.T.; Xiao, D.X.; Li, Z.S.; Cheng, J.L.; Fang, S.W.; Du, Y.J.; Zhao, J.-H.; Dong, X.W.; Zhu, G.N. Design, synthesis, and fungicidal evaluation of novel pyrazole-furan and pyrazole-pyrrole carboxamide as succinate dehydrogenase inhibitors. J. Agric. Food Chem. 2017, 65, 5397–5403. [Google Scholar] [CrossRef]
- 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. Discovery of Novel Succinate Dehydrogenase Inhibitors by the Integration of in Silico Library Design and Pharmacophore Mapping. J. Agric. Food Chem. 2017, 65, 3204–3211. [Google Scholar] [CrossRef] [PubMed]
- Wang, B.L.; Wang, H.X.; Liu, H.; Xiong, L.; Yang, N.; Zhang, Y.; Li, Z.M. Synthesis and structure-insectidical relationship of novel phenylpyrazole carboxylic acid dervatives containing fluorine moiety. Chin. Chem. Lett. 2020, 31, 739–745. [Google Scholar] [CrossRef]
- Xue, H.S.; Liu, A.P.; Liu, W.D.; Li, J.M.; Ren, Y.G.; Huang, L.; He, L.; Ou, X.M.; Ye, J.; Huang, M.Z. Syntheses and fungicidal activities of thiazole-5-carboxanilides bearing thioether group. Chem. Res. Chin. Univ. 2016, 32, 781–785. [Google Scholar] [CrossRef]
- King, W.F.; Wheeler, R.E. Substituted Oxadiazoles and Their Use as Corn Root Worm Insecticides. US Patent US4237121A, 2 December 1981. [Google Scholar]
- Liu, Q.; Zhu, R.; Gao, S.; Ma, S.H.; Tang, H.J.; Diao, Y.M.; Wang, H.L.; Zhu, H.J. Structure-based bioisosterism design, synthesis, insecticidal activity and structure-activity relationship (SAR) of anthranilic diamide analogues containing 1,2,4-oxadiazole rings. Pest Manage. Sci. 2017, 73, 917–924. [Google Scholar] [CrossRef]
- Haugwitz, R.D.; Martinez, A.J.; Venslavsky, J.; Angel, R.G.; Maurer, B.V.; Jacobs, G.A.; Narayanan, V.L.; Cruthers, L.R.; Szanto, J. Synyhesis and anthelmintic acyivities of novel isothiocyanatophenyl-1,2,4-oxadiazoles. J. Med. Chem. 1985, 28, 1234–1241. [Google Scholar] [CrossRef]
- Terteryan-Seiser, V.; Grammenos, W.; Wiebe, C.; Kretschmer, M.; Craig, I.R.; Escribano, C.A.; Marcus, F.; Tobias, M.; Palomar, M.A.Q.; Grote, T.; et al. Substituted Oxadiazoles for Combating Phytopathogenic Fungi. WO Patent WO2017178245A1, 19 October 2017. [Google Scholar]
- Iwata, J.; Nakamura, Y.; Hayashi, T.; Watanabe, S.; Sano, H. Oxadiazole Compound and Fungicide for Agricultural and Horticultural Use. WO Patent WO2019022061A1, 31 January 2019. [Google Scholar]
- Ryu, E.K.; Chung, K.H.; Lee, W.H.; Kim, J.N.; Hong, K.S. Herbicidal Quinolinyloxadiazoles. WO Patent WO9404530A1, 3 March 1994. [Google Scholar]
- Feng, M.L.; Li, Y.F.; Zhu, H.J.; Zhao, L.; Xi, B.B.; Ni, J.P. Synthesis, Insecticidal Activity, and Structure-Activity Relationship of Trifluoromethyl-Containing Phthalic Acid Diamide Structures. J. Agric. Food Chem. 2010, 58, 10999–11006. [Google Scholar] [CrossRef] [PubMed]
- Liu, M.; Wang, Y.; Wangyang, W.Z.; Liu, F.; Cui, Y.L.; Duan, Y.S.; Wang, M.; Liu, S.Z.; Rui, C.H. Design, Synthesis, and Insecticidal Activities of Phthalamides Containing a Hydrazone Substructure. J. Agric. Food Chem. 2010, 58, 6858–6863. [Google Scholar] [CrossRef]
- Lahm, G.P.; Stevenson, T.M.; Selby, T.P.; Freudenberger, J.H.; Cordova, D.; Flexner, L.; Bellin, C.A.; Dubas, C.M.; Smith, B.K.; Hughes, K.A.; et al. RynaxypyrTM: A new insecticidal anthranilic diamide that acts as a potent and selective ryanodine receptor activator. Bioorg. Med. Chem. Lett. 2007, 17, 6274–6279. [Google Scholar] [CrossRef]
- Hughes, K.A.; Lahm, G.P.; Selby, T.P.; Stevenson, T.M. Cyano Anthranilamide Insecticides. WO Patent WO2004067528A1, 21 January 2004. [Google Scholar]
- Clark, D.A.; Lahm, G.P.; Smith, B.K.; Barry, J.D.; Clagg, D.G. Synthesis of insecticidal fluorinated anthranilic diamides. Bioorg. Med. Chem. 2008, 16, 3163–3170. [Google Scholar] [CrossRef] [PubMed]
- Wu, J.; Song, B.A.; Hu, D.Y.; Yue, M.; Yang, S. Design, synthesis and insecticidal activities of novel pyrazole amides containing hydrazone substructures. Pest Manag. Sci. 2012, 68, 801–810. [Google Scholar] [CrossRef] [PubMed]
- Zhang, J.F.; Xu, J.Y.; Wang, B.L.; Li, Y.X.; Xiong, L.X.; Li, Y.Q.; Ma, Y.; Li, Z.M. Synthesis and insecticidal activities of novel anthranilic diamides containing acylthiourea and acylurea. J. Agric. Food Chem. 2012, 60, 7565–7572. [Google Scholar] [CrossRef]
- Chen, K.; Liu, Q.; Ni, J.P.; Zhu, H.J.; Li, Y.F.; Wang, Q. Synthesis: Insecticidal activities and structureactivity relationship studies of novel anthranilic diamides containing pyridylpyrazole-4-carboxamide. Pest Manag. Sci. 2015, 71, 1503–1512. [Google Scholar] [CrossRef] [PubMed]
- Hua, X.W.; Mao, W.T.; Fan, Z.J.; Ji, X.T. Novel anthranilic diamide insecticides: Design, synthesis, and insecticidal evaluation. Aust. J. Chem. 2014, 67, 1491–1503. [Google Scholar] [CrossRef]
- Zhou, S.; Jia, Z.H.; Xiong, L.X.; Yan, T.; Yang, N.; Wu, G.; Song, H.; Li, Z. Chiral dicarboxamide scaffolds containing a sulfiliminyl moiety as potential ryanodine receptor activators. J. Agric. Food Chem. 2014, 62, 6269–6277. [Google Scholar] [CrossRef]
- Zhou, S.; Gu, Y.C.; Liu, M.; Wu, C.; Zhou, S.; Zhao, Y.; Jia, Z.; Wang, B.; Xiong, L.; Yang, N.; et al. Insecticidal activities of chiral N-trifluoroacetyl sulfilimines as potential ryanodine receptor modulators. J. Agric. Food Chem. 2014, 62, 11054–11061. [Google Scholar] [CrossRef] [PubMed]
- Amarasekare, K.G.; Shearer, P.W. Comparing effects of insecticides on two green lacewings species Chrysoperla johnsoni and Chrysoperla carnea (Neuroptera: Chrysopidae). J. Econ. Entomol. 2013, 106, 1126–1133. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schmidt, R.A.; Beers, E.H. Impacts of orchard pesticides on Galendromus occidentalis: Lethal and sublethal effects. Crop Prot. 2013, 56, 16–24. [Google Scholar]
- Kohara, Y.; Kubo, K.; Imamiya, E.; Wada, T.; Inada, Y.; Naka, T. Synthesis and angiotensin II receptor antagonistic activities of benzimidazole derivatives bearing acidic heterocycles as novel tetrazole bioisosteres. J. Med. Chem. 1996, 39, 5228–5235. [Google Scholar] [CrossRef]
- Tagad, H.D.; Hamada, Y.; Nguyen, J.T.; Hamada, T.; Abdel-Rahman, H.; Yamani, A.; Nagamine, A.; Ikari, H.; Igawa, N.; Hidaka, K.; et al. Design of pentapeptidic BACE1 inhibitors with carboxylic acid bioisosteres at P1’ and P4 positions. Bioorg. Med. Chem. 2010, 18, 3175–3186. [Google Scholar] [CrossRef] [PubMed]
- Yang, S.; Tian, X.Y.; Liu, X.H.; Tan, C.X. Synthesis and Biological Activity of Benzamides Substituted with Pyridine-Linked 1,2,4-Oxadiazole. Molecules 2020. [Google Scholar] [CrossRef] [PubMed]
- Dey, S.; Mal, D. Total synthesis of BE-23254, a chlorinated angucycline antibiotic. Tetrahedron Lett. 2005, 46, 5483–5486. [Google Scholar] [CrossRef]
- Zhang, Y.; Zhu, H.W.; Shang, J.F.; Wang, B.L.; Li, Z.M. Synthesis and Biological Activities of Novel 3-(((3-Bromo1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl) methylene) amino)-substituted-benzo [d] [1–3] triazin-4(3H)-ones. Chin. J. Org. Chem. 2019, 39, 861–866. [Google Scholar] [CrossRef]
- Mu, J.X.; Shi, Y.X.; Yang, M.Y.; Sun, Z.H.; Liu, X.H.; Li, B.J.; Sun, N.B. Design, Synthesis, DFT Study and Antifungal Activity of Pyrazolecarboxamide Derivatives. Molecules 2016, 21, 68. [Google Scholar] [CrossRef] [Green Version]
- Zhang, Y.; Wang, X.; Yin, X.; Wang, H. Toxicity assessment of combined fluoroquinolone and tetracycline exposure in zebrafish (Danio rerio). Environ. Toxicol. Pharmacol. 2016, 31, 736–750. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, Y.H.; Liu, M.; Liu, J.F.; Wang, X.; Wang, C.; Ai, W.; Chen, S.; Wang, H. Combined toxicity of triclosan 1,2,4-dichlorophenol and 2,4,6-trichlorophenol to zebrafish (Danio rerio). Environ. Toxicol. Pharmacol. 2018, 57, 9–18. [Google Scholar] [CrossRef] [PubMed]
Compound | R | Insecticidal Activities (500 mg/L, Death Rates %) | Fungicidal Activities (100 mg/L, Inhibition Rates %) | |||
---|---|---|---|---|---|---|
Mythimna sepatara | Botrytis cinereal | Fusarium graminearum | Marssonina mali | Thanatephorus cucumeris | ||
9a | H | 10 | 48.2 | 0 | 22.0 | 0 |
9b | 2-CH3 | 5 | 25.0 | 2.4 | 15.3 | 0 |
9c | 4-CH3 | 20 | 48.2 | 0.9 | 13.5 | 0 |
9d | 4-t-Bu | 0 | 18.5 | 18.2 | 16.5 | 0 |
9e | 2,4-di-CH3 | 30 | 57.7 | 2.9 | 10.6 | 0 |
9f | 3-CF3 | 25 | 63.5 | 8.5 | 16.5 | 0 |
9g | 3-Cl-2-CH3 | 15 | 65.9 | 0 | 10.0 | 0 |
9h | 2-F | 30 | 57.1 | 5.3 | 20.9 | 0 |
9i | 4-F | 10 | 23.5 | 6.8 | 16.8 | 0 |
9j | 2,6-di-F | 0 | 19.7 | 16.2 | 21.5 | 0 |
9k | 2-Cl | 5 | 61.2 | 15.0 | 14.4 | 0 |
9l | 3-Cl | 0 | 20.9 | 17.4 | 24.4 | 0 |
9m | 4-Cl | 5 | 5.3 | 0 | 12.4 | 0 |
9n | 4-Br | 25 | 17.7 | 4.7 | 18.5 | 0 |
10a | H | 20 | 84.4 | 25.0 | 39.2 | 0 |
10b | 2-CH3 | 15 | 80.8 | 29.4 | 37.8 | 0 |
10c | 4-CH3 | 10 | 22.9 | 53.1 | 34.1 | 0 |
10d | 4-t-Bu | 25 | 83.6 | 52.5 | 44.2 | 44.2 |
10e | 2,4-di-CH3 | 35 | 83.3 | 46.4 | 39.4 | 41.9 |
10f | 3-CF3 | 40 | 83.1 | 43.6 | 45.8 | 37.5 |
10g | 3-Cl-2-CH3 | 25 | 81.1 | 50.0 | 42.8 | 44.7 |
10h | 2-F | 40 | 81.4 | 51.4 | 48.3 | 50.3 |
10i | 4-F | 25 | 83.3 | 54.4 | 43.1 | 44.2 |
10j | 2,6-di-F | 15 | 31.8 | 23.2 | 38.8 | 0 |
10k | 2-Cl | 5 | 81.9 | 50.3 | 45.0 | 46.1 |
10l | 3-Cl | 15 | 83.6 | 48.1 | 39.2 | 44.4 |
10m | 4-Cl | 15 | 22.7 | 13.2 | 33.2 | 0 |
10n | 4-Br | 20 | 17.9 | 11.8 | 37.1 | 0 |
Broflanilide | 100 | nt | nt | nt | nt | |
Chlorantraniliprole | 100 | nt | nt | nt | nt | |
Pyraclostrobin | nt | 81.4 | 100 | 84.1 | 100 |
Compound | y = a + bx | r2 | EC50/(μg mL−1) |
---|---|---|---|
10f | y = 1.5374x + 3.2171 | 0.9961 | 14.44 |
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Yang, S.; Ren, C.-L.; Ma, T.-Y.; Zou, W.-Q.; Dai, L.; Tian, X.-Y.; Liu, X.-H.; Tan, C.-X. 1,2,4-Oxadiazole-Based Bio-Isosteres of Benzamides: Synthesis, Biological Activity and Toxicity to Zebrafish Embryo. Int. J. Mol. Sci. 2021, 22, 2367. https://doi.org/10.3390/ijms22052367
Yang S, Ren C-L, Ma T-Y, Zou W-Q, Dai L, Tian X-Y, Liu X-H, Tan C-X. 1,2,4-Oxadiazole-Based Bio-Isosteres of Benzamides: Synthesis, Biological Activity and Toxicity to Zebrafish Embryo. International Journal of Molecular Sciences. 2021; 22(5):2367. https://doi.org/10.3390/ijms22052367
Chicago/Turabian StyleYang, Sen, Chao-Li Ren, Tian-Yang Ma, Wen-Qian Zou, Li Dai, Xiao-Yu Tian, Xing-Hai Liu, and Cheng-Xia Tan. 2021. "1,2,4-Oxadiazole-Based Bio-Isosteres of Benzamides: Synthesis, Biological Activity and Toxicity to Zebrafish Embryo" International Journal of Molecular Sciences 22, no. 5: 2367. https://doi.org/10.3390/ijms22052367