Synthesis, Biological Activity and Three-Dimensional Quantitative Structure-Activity Relationship (3D-QSAR) Study of Novel 4-Methyl-1,2,4-triazole-thioethers Containing gem-Dimethylcyclopropane Ring

doi:10.6023/cjoc201912042

Chinese Journal of Organic Chemistry ›› 2020, Vol. 40 ›› Issue (6): 1647-1657.DOI: 10.6023/cjoc201912042 Previous Articles Next Articles

新型含偕二甲基环丙烷的4-甲基-1,2,4-三唑硫醚化合物的合成、生物活性及三维定量构效关系(3D-QSAR)研究

虞友培^a, 段文贵^a, 林桂汕^a, 康国强^a, 王晓宇^a, 雷福厚^b

a 广西大学化学化工学院南宁 530004;
b 广西民族大学广西林产化学与工程重点实验室南宁 530008

收稿日期:2019-12-28 修回日期:2020-02-27 发布日期:2020-03-11
通讯作者: 段文贵 E-mail:wgduan@gxu.edu.cn
基金资助:
国家自然科学基金（No.31870556）和广西科技基地和人才专项（No.AD18126005）资助项目.

Synthesis, Biological Activity and Three-Dimensional Quantitative Structure-Activity Relationship (3D-QSAR) Study of Novel 4-Methyl-1,2,4-triazole-thioethers Containing gem-Dimethylcyclopropane Ring

Yu Youpei^a, Duan Wengui^a, Lin Guishan^a, Kang Guoqiang^a, Wang Xiaoyu^a, Lei Fuhou^b

a College of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004;
b Guangxi Key Laboratory of Chemistry and Engineering of Forest Products, Guangxi University for Nationalities, Nanning 530008

Received:2019-12-28 Revised:2020-02-27 Published:2020-03-11
Supported by:
Project supported by the National Natural Science Foundation of China (No. 31870556) and the Specific Research Project of Guangxi for Research Bases and Talents (No. AD18126005).

1. 201647S.pdf(2665KB)

Abstract

A series of novel 4-methyl-1,2,4-triazole-thioethers containing gem-dimethylcyclopropane ring were designed and synthesized by multi-step reactions in search of potent novel bioactive molecules. Structures of all the target compounds were characterized by means of UV-Vis, FTIR, NMR, ESI-MS, and elemental analysis. The antifungal and herbicidal activities of the target compounds were preliminarily evaluated. As indicated in bioassay results, 2 compounds exhibited excellent antifungal activity against Physalospora piricola, which are much better than that of the commercial fungicide of chlorothalonil used as positive control. Also, at 100 μg/mL, 4 compounds displayed prominent herbicidal activity against the root-growth of rape (Brassica campestris), which are much better than that of the commercial herbicide of flumioxazin used as positive control. In the interest of developing more effective antifungal compounds against P. piricola, the preliminary analysis of three-dimen-sional quantitative structure-activity relationship (3D-QSAR) was carried out using the molecular field analysis (CoMFA) method, and a reasonable and effective 3D-QSAR model (r²=0.985, q²=0.509) has been established.

Key words: gem-dimethylcyclopropane, 3-carene, 1,2,4-triazole-thioether, biological activity, three-dimensional quantitative structure-activity relationship (3D-QSAR)

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Yu Youpei, Duan Wengui, Lin Guishan, Kang Guoqiang, Wang Xiaoyu, Lei Fuhou. Synthesis, Biological Activity and Three-Dimensional Quantitative Structure-Activity Relationship (3D-QSAR) Study of Novel 4-Methyl-1,2,4-triazole-thioethers Containing gem-Dimethylcyclopropane Ring[J]. Chinese Journal of Organic Chemistry, 2020, 40(6): 1647-1657.

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[1] Karapandzova, M.; Stefkov, G.; Karanfilova, I. C.; Panovska, T. K.; Stanoeva, J. P.; Stefova, M.; Kulevanova, S. Rec. Nat. Prod. 2018, 13, 50.
[2] Cao, J. Q.; Guo, S. S.; Wang, Y.; Pang, X.; Geng, Z. F.; Du, S. S. Ecotoxicol. Environ. Saf. 2018, 160, 342.
[3] Basholli-Salihu, M.; Schuster, R.; Hajdari, A.; Mulla, D.; Viernstein, H.; Mustafa, B.; Mueller, M. Pharm. Biol. 2017, 55, 1553.
[4] Smeriglio, A.; Denaro, M.; Barreca, D.; Calderaro, A.; Bisignano, C.; Ginestra, G.; Bellocco, E.; Trombetta, D. Int. J. Mol. Sci. 2017, 18, 1212.
[5] Cutillas, A. B.; Carrasco, A.; R, M. G.; Tomas, V.; Tudela, J. Plant Biosyst. 2018, 152, 1282.
[6] da Silva, B. G.; Fileti, A. M. F.; Foglio, M. A.; Ruiz, A. L. T. G.; Rosa, P. D. V. E. J. Supercrit. Fluids 2017, 130, 10.
[7] Kang, G. Q.; Duan, W. G.; Lin, G. S.; Yu, Y. P.; Wang, X. Y.; Lu, S. Z. Molecules 2019, 24, 477.
[8] Inoue, Y.; Ohono, S.; Mizuno, T.; Yura, Y.; Murayama, K. In Synthetic Pyrethroids, Vol. 42, Ed.:Elliott M., American Chemical Society, Washington DC, 1977, p. 72.
[9] Horáková, E.; Drabina, P.; Brož, B.; Štěpánková, Š.; Vorčáková, K.; Královec, K.; Havelek, R.; Sedlák, M. J. Enzyme Inhib. Med. Chem. 2017, 31, 173.
[10] Ghosh, A. K.; Reddy, G. C.; Kovela, S.; Relitti, N.; Urabe, V. K.; Prichard, B. E.; Jurica, M. S. Org. Lett. 2018, 20, 7293.
[11] Pieroni, M.; Annunziato, G.; Azzali, E.; Dessanti, Paola.; Mercurio, C.; Meroni, G.; Trifiró, P.; Vianello, P.; Villa, M.; Beato, C.; Varasi, M.; Costantino, G. Eur. J. Med. Chem. 2015, 92, 377.
[12] Sampson, P. B.; Liu, Y.; Patel, N. K.; Feher, M.; Forrest, B.; Li, S. W.; Edwards, L.; Laufer, R.; Lang, Y.; Ban, F.; Awrey, D. E.; Mao, G.; Plotnikova, O.; Leung, G.; Hodgson, R.; Mason, J.; Wei, X.; Kiarash, R.; Green, E.; Qiu, W.; Chirgadze, N. Y.; Mak, T. W.; Pan, G.; Pauls, H. W. J. Med. Chem. 2014, 58, 130.
[13] Okamoto, K.; Kodama, K.; Takase, K.; Sugi, N. H.; Yamamoto, Y.; Iwata, M.; Tsuruoka, A. Cancer Lett. 2013, 340, 97.
[14] Burmudžija, A. Z.; Muškinja, J. M.; Kosanić, M. M.; Ranković, B. R.; Novaković, S. B.; Đorđević, S. B.; Stanojković, T. P.; Baskić, D. D.; Ratković, Z. R. Chem. Biodiversity 2017, 14, e1700077.
[15] Liu, X. H.; Shi, Y. X.; Ma, Y.; Zhang, C. Y.; Dong, W. L.; Pan, L.; Wang, B. L.; Li, B. J.; Li, Z. M. Eur. J. Med. Chem. 2009, 44, 2782.
[16] Moussa, B. A.; El-Zaher, A. A.; El-Ashrey, M. K.; Fouad, M. A. Eur. J. Med. Chem. 2018, 148, 477.
[17] Zhu, Y. Q.; Zhang, J.; Yuan, Y. W.; Xie, L. F.; Xu, H. Z.; Zou, X. M.; Yang, H. Z. J. Heterocycl. Chem. 2013, 50, 202.
[18] Lin, G. S.; Duan, W. G.; Yang, L. X.; Huang, M.; Lei, F. H. Molecules 2017, 22, 193.
[19] Zhao, B.; Fan, S. J.; Fan, Z. J.; Wang, H. X.; Zhang, N. L.; Guo, X. F.; Yang, D. Y.; Wu, Q. F; Yu, B.; Zhou, S. J. Agric. Food. Chem. 2018, 66, 12439.
[20] 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.
[21] Wang, X. B.; Zhong, X. M.; Zhu, X. S.; Wang, H.; Qin, L.; Zhang, J. P.; Ruan, X. H.; Wei, X. Chem. Pap. 2017, 71, 1953.
[22] Du, H.; Fan, Z. J; Yang, L.; Bao, X. P. Mol. Diversity 2018, 22, 1.
[23] Pokharia, M.; Yadav, S. K.; Mishra, H.; Pandey, N.; Tilak, R.; Pokharia, S. J. Mol. Struct. 2017, 1144, 324.
[24] Wang, T.; Ueda, Y.; Zhang, Z. X.; Yin, Z. W.; Matiskella, J.; Pearce, B. C.; Yang, Z.; Zheng, M.; Parker, D. D.; Yamanaka, G. A.; Gong, Y. F.; Ho, H-T.; Colonno, R. J.; Langley, D. R.; Lin, P-F.; Meanwell, N. A.; Kadow, J. F. J. Med. Chem. 2018, 61, 6308.
[25] Timur, İ.; Kocyigit, Ü. M.; Dastan, T.; Sandal, S.; Ceribası, A. O.; Taslimi, P.; Gulcin, İ.; Koparir, M.; Karatepe, M.; Çiftçi, M. J. Biochem. Mol. Toxicol. 2019, 33, 1.
[26] Kulabaş, N.; Tatar, E.; Bingölözakpinar, ö.; özsavci, D.; Pannecouque, C.; De Clercq, E.; Kücükgüzel, I. Eur. J. Med. Chem. 2016, 121, 58.
[27] Shanmugapriya, A.; Dallemer, F.; Prabhakaran, R. New J. Chem. 2018, 42, 18850.
[28] Pillai, R. R.; Karrouchi, K.; Fettach, S.; Armaković, S.; Armaković, S. J.; Brik, Y.; Taoufik, J.; Radi, S.; El Abbes Faouzi, M.; Ansar, M. H. J. Mol. Struct. 2019, 1177, 47.
[29] Shang, J.; Wang, W. M.; Li, Y. H.; Song, H. B.; Li, Z. M.; Wang, J. G. J. Agric. Food. Chem. 2012, 60, 8286.
[30] Liu, X. H.; Zhai, Z. W.; Xu, X. Y.; Yang, M. Y.; Sun, Z. H.; Weng, J. Q.; Tan, C. X.; Chen, J. Bioorg. Med. Chem. Lett. 2015, 25, 5524.
[31] Wang, B. L.; Shi, Y. X.; Ma, Y.; Liu, X. H.; Li, Y. H.; Song, H. B.; Li, B. J.; Li, Z. M., J. Agric. Food. Chem 2010, 58, 5515.
[32] Huang, M.; Duan, W. G.; Lin, G. S.; Li, K.; Hu, Q. Molecules 2017, 22, 1538.
[33] Hu, Q.; Lin, G. S.; Duan, W. G.; Huang, M.; Lei, F. H. Molecules 2017, 22, 1678.
[34] Li, F. Y.; Wang, X.; Duan, W. G.; Lin, G. S. Molecules 2017, 22, 1087.
[35] Lin, G. S.; Chen, Z. C.; Duan, W. G.; Wang, X. Y.; Lei, F. H. Chin. J. Org. Chem. 2018, 38, 2085(in Chinese). (林桂汕, 陈智聪, 段文贵, 王晓宇, 雷福厚, 有机化学, 2018, 38, 2085.)
[36] Chen, N. Y.; Duan, W. G.; Lin, G. S.; Liu, L. Z.; Zhang, R.; Li, D. P. Mol. Diversity 2016, 20, 897.
[37] Verma, J.; Khedkar, M. V.; Coutinho, E. C. Curr. Top. Med. Chem. 2010, 10, 95.
[38] Thareja, S. Chem. Rev. 2015, 115, 2883.
[39] Nair, L. G.; Saksena, A.; Lovey, R.; Sannigrahi, M.; Wong, J.; Kong, J. S.; Fu, X. Y.; Girijavallabhan, V. J. Org. Chem. 2010, 75, 1285.
[40] Yu, Y. P.; Duan, W. G.; Lin, G. S.; Kang, G. Q.; Wang, X. Y.; Cen, B.; Lei, F. H. Chin. J. Syn. Chem. 2019, 27, 689. (虞友培, 段文贵, 林桂汕, 康国强, 王晓宇, 岑波, 雷福厚, 合成化学, 2019, 27, 689.)
[41] Su, N. N.; Yao, L.; Yu, S. J.; Zhang, X.; Liu, X. H.; Zhao, W. G. Res. Chem. Intermed. 2013, 39, 759.

新型含偕二甲基环丙烷的4-甲基-1,2,4-三唑硫醚化合物的合成、生物活性及三维定量构效关系(3D-QSAR)研究

Synthesis, Biological Activity and Three-Dimensional Quantitative Structure-Activity Relationship (3D-QSAR) Study of Novel 4-Methyl-1,2,4-triazole-thioethers Containing gem-Dimethylcyclopropane Ring

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