以环丙烷限制构象的新型双酰胺的设计、合成、抗癌活性及计算分析
收稿日期: 2021-06-29
修回日期: 2021-08-02
网络出版日期: 2021-09-03
基金资助
国家重点研发计划(2017YFD0200505)
Design, Synthesis, Anti-cancer Activities and Computational Analysis of Novel Diamides Conformationally Restricted by Cyclopropane
Received date: 2021-06-29
Revised date: 2021-08-02
Online published: 2021-09-03
Supported by
National Key Research Program of China(2017YFD0200505)
为了探索具有新型骨架的抗癌剂, 设计了一系列的以环丙烷限制构象的双酰胺类化合物. 大多数含有顺式环丙烷中心的外消旋体对四种肿瘤细胞系(MCF-7、BGC-823、HepG2和NCI-H460)具有良好的抑制活性. 其中, 消旋体顺式-N1-(2-甲基-4-(全氟丙-2-基)苯基)-N2-(4-苯氧基苄基)环丙烷-1,2-二羧酰胺(1-19)对MCF-7的IC50值为(8.38±0.67) mg•L–1, 显示出可进一步优化为抗癌先导物的潜力. 此外, 甾醇硫酸酯酶(steryl-sulfatase, STS)被PharmMapper预测为可能的靶标蛋白, 并由分子对接实验进行了验证.
陈睿嘉 , 周聪 , 逄锡文 , 刘佳君 , 顾玉诚 , 刘建文 , 李忠 . 以环丙烷限制构象的新型双酰胺的设计、合成、抗癌活性及计算分析[J]. 有机化学, 2022 , 42(1) : 277 -292 . DOI: 10.6023/cjoc202106053
A series of diamides conformationally restricted by cyclopropane were designed and synthesized. Most of the racemates containing cis-cyclopropane possessed promising inhibitory activity against four cancer cell lines (MCF-7, BGC-823, HepG2 and NCI-H460). In particular, racemate cis-N1-(2-methyl-4-(perfluoropropan-2-yl)phenyl)-N2-(4-phenoxy- benzyl)cyclopropane-1,2-dicarboxamide (1-19) showed the potential for further optimization as an anti-cancer lead with the IC50 value of (8.38±0.67) mg•L–1 on MCF-7. Moreover, steryl-sulfatase (STS) was predicated as the potential target protein and molecular docking was performed to explore the binding mode.
Key words： diamides; cyclopropane; anti-cancer activities; target prediction; docking
| [1] | Torre, L. A.; Bray, F.; Siegel, R. L.; Ferlay, J.; Lortet-Tieulent, J.; Jemal, A. CA-Cancer J. Clin. 2015, 65, 87. |
| [2] | Sung, H.; Ferlay, J.; Siegel, R. L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. CA-Cancer J. Clin. 2021, 71, 209. |
| [3] | Dickens, E.; Ahmed, S. Surgery (Oxford) 2018, 36, 134. |
| [4] | Jagoe, K. N. R. T.; Abalo, R. Front. Pharmacol. 2018, 9, 245. |
| [5] | Janganati, V.; Ponder, J.; Thakkar, S.; Thakkar, S.; Jordan, C. T.; Crooks, P. A. Bioorg. Med. Chem. 2017, 25, 3694. |
| [6] | Pattabiraman, V. R.; Bode, J. W. Nature 2011, 480, 471. |
| [7] | Kumari, S.; Carmona, A. V.; Tiwari, A. K.; Trippier, P. C. J. Med. Chem. 2020, 63, 12290 |
| [8] | Vlaar, C. P.; Castillo-Pichardo, L.; Medina, J. I.; Marrero-Serra, C. M.; Vélez, E; Ramos, Z.; Hernández, E. Bioorg. Med. Chem. 2018, 26, 884. |
| [9] | Rai, U. S.; Isloor, A. M.; Shetty, P.; Pai, K. S. R.; Fun, H. K. Arabian J. Chem. 2015, 8, 317. |
| [10] | Shao, P. P.; Ok, D.; Fisher, M. H.; Garcia, M. L.; Kaczorowski, G. J.; Li, C.; Lyons, K. A.; Martin, W. J.; Meinke, P. T.; Priest, B. T.; Smith, M. M.; Wyvratt, M. J.; Ye, F.; Parsons, W. H. Bioorg. Med. Chem. Lett. 2005, 15, 1901. |
| [11] | Tarzia, G.; Shiatti, P.; Selva, D.; Favara, D.; Ceriani, S. Eur. J. Med. Chem. 1976, 11, 263. |
| [12] | Hickey, S. M.; Ashton, T. D.; Khosa, S. K.; Robson, R. N.; White, J. M.; Li, J.; Nation, R. L.; Yu, H. Y.; Elliott, A. G.; Butler, M. S.; Huang, J. X.; Cooper, M. A.; Pfeffer, F. M Org. Biomol. Chem. 2015, 22, 6255. |
| [13] | Saudi, M.; Zmurko, J.; Kaptein, S.; Rpzenski, J.; Gadakh, B.; Chaltin, P.; Marchand, A.; Neyts, J.; Aerschot, A. V. Eur. J. Med. Chem. 2016, 12, 158. |
| [14] | Tohnishi, M.; Nakao, H.; Furuya, T.; Seo, A.; Kodama, H.; Tsubata, K.; Fujioka, S.; Kodama, H.; Hirooka, T.; Nishimatsu, T. J. Pestic. Sci. 2005, 30, 354. |
| [15] | Galano, A.; Alvarez-Idaboy, J. R.; Vivier-Bunge, A. Theor. Chem. Acc. 2007, 118, 597. |
| [16] | Talele, T. T. J. Med. Chem. 2016, 59, 8712. |
| [17] | Julius, D. A. Am. J. Psychiatry 1979, 136, 782. |
| [18] | Yakes, F. M.; Chen, J.; Tan, J.; Yamaguchi, K.; Shi, Y.; Yu, P.; Qian, F.; Chu, F.; Bentzien, F.; Cancilla, B.; Orf, J.; You, A.; Laird, A. D.; Engst, S.; Lee, L.; Lesch, J.; Chou, Y.-C.; Joly, A. H. J. Clin. Oncol. 2017, 35, 591. |
| [19] | Chopra, N.; Nathan, P. D. Expert Rev. Anticancer Ther. 2015, 15, 749. |
| [20] | Scheciiter, M. S.; Sullivan, W. N.; Schoof, H. F.; Maddock, D. R.; Amyx, C. M.; Porter, J. E. J. Med. Entomol. 1974, 11, 231. |
| [21] | Matsui, K.; Kido, Y.; Watari, R.; Kashima, Y.; Yoshida, Y.; Shuto, S. Chem. Eur. J. 2017, 23, 3034. |
| [22] | Lavedan, C.; Forsberg, M.; Gentile, A. J. Neuropharmacology 2015, 91, 142. |
| [23] | Yamaguchi, K.; Kazuta, Y.; Hirano, K.; Yamada, S.; Matsuda, A.; Shuto, S. Bioorg. Med. Chem. 2008, 16, 8875. |
| [24] | Martin, S. F.; Dorsey, G. O.; Gane, T.; Hillier, M. C.; Kessler, H.; Baur, M.; Mathä, B.; Erickson, J. W.; Bhat, T. N.; Munshi, S.; Gulnik, S. V.; Topol, I. A. J. Med. Chem. 1998, 41, 1581. |
| [25] | Chen, Y.; Le, V.; Xu, X.; Shao, X.; Liu, J.; Li, Z. Bioorg. Med. Chem. Lett. 2014, 24, 3948. |
| [26] | Ozoe, Y.; Kita, T.; Ozoe, F.; Nakao, T.; Sato, K.; Hirase, K. Pestic. Biochem. Physiol. 2013, 107, 285. |
| [27] | Shang, J.; Liu, Q.; Wang, B.; Li, Z. Chin. J. Org. Chem. 2019, 39, 1489. (in Chinese) |
| [27] | (尚俊峰, 刘巧霞, 王宝雷, 李正名, 有机化学, 2019, 39, 1489.) |
| [28] | Chen, K.; Liu, Q.; Ni, J.; Zhu, H.; Li, Y.; Wang, Q. Pest Manage. Sci. 2014, 71, 1503. |
| [29] | Duan, J. J.-W.; Lu, Z.; Jiang, B.; Stachura, S.; Weigelt, C. A.; Sack, J. S.; Khan, J.; Ruzanov, M.; Galella, M. A.; Wu, D.-R.; Yarde, M.; Shen, D.-R.; Shuster, D. J.; Borowski, V.; Xie, J. H.; Zhang, L.; Vanteru, S.; Gupta, A. K.; Mathur, A.; Zhao, Q.; Foster, W.; Salter-Cid, L. M.; Carter, P. H.; Dhar, T. G. M. ACS Med. Chem. Lett. 2019, 10, 367. |
| [30] | Li, Z.; Xu, X.; Chen, Y.; Liu, J.; Li, W. CN 103435562, 2013. (in Chinese) |
| [31] | Li, Z.; Chen, Y.; Liu, A.; Li, Y.; Wang, B.; Pan, L.; Wan, Y.; Liu, J.; Chen, W. CN 104402785, 2015. (in Chinese) |
| [32] | Lepri, S.; Goracci, L.; Valeri, A.; Cruciani, G. Eur. J. Med. Chem. 2016, 121, 658. |
| [33] | Simpkins, L. M.; Bolton, S.; Pi, Z.; Sutton, J. C.; Kwon, C.; Zhao, G.; Magnin, D. R.; Augeri, D. J.; Gungor, T.; Rotella, D. P.; Sun, Z.; Liu, Y.; Slusarchyk, W. S.; Marcinkeviciene, J.; Robertson, J. G.; Wang, A.; Robl, J. A.; Atwal, K. S.; Zahler, R. L.; Parker, R. A.; Kirby, M. S.; Hamann, L. G. Bioorg. Med. Chem. Lett. 2007, 17, 6476. |
| [34] | Wang, F.; Xu, X. Wang, F; Peng, L.; Zhang, Y.; Wang, L.; Wang, L. Lett. Org. Chem. 2015, 12, 741. |
| [35] | Milewska, M. J.; Gdaniec, M.; Poloński, T. Tetrahedron: Asymmetry 1996, 7, 3169. |
| [36] | Beutner, G. L.; Young, I. S.; Davies, M. L.; Hickey, M. R.; Park, H.; Stevens, J. M.; Ye, Q. Org. Lett. 2018, 20, 4218. |
| [37] | Liu, X.; Ouyang, S.; Yu, B.; Liu, Y.; Huang, K.; Gong, J.; Zheng, S.; Li, Z.; Li, H.; Jiang, H. Nucleic Acids Res. 2010, 38, 609. |
| [38] | Wang, X.; Pan, C.; Gong, J.; Liu, X.; Li, H. J. Chem. Inf. Model. 2016, 56, 1175. |
| [39] | Wang, X.; Shen, Y.; Wang, S.; Li, S.; Zhang, W.; Liu, X.; Lai, L.; Pei, J.; Li, H. Nucleic Acids Res. 2017, 45, 356. |
| [40] | Ferrante, P.; Messali, S.; Meroni, G.; Ballabio, A. Eur. J. Hum. Genet. 2002, 10, 813. |
| [41] | Hernandez-Guzman, F. G.; Higashiyama, T.; Pangborn, W.; Osawa, Y.; Ghosh, D. J. Biol. Chem. 2003, 278, 22989. |
| [42] | Geisler, J.; Sasano, H.; Chen, S.; Purohit, A. J. Steroid Biochem. Mol. Biol. 2011, 125, 39. |
| [43] | Purohit, A.; Foster, P. A. J. Endocrinol. 2012, 212, 99. |
| [44] | Leese, M. P.; Hejaz, H. A. M.; Mahon, M. F.; Newman, S. P.; Purohit, A.; Reed, M. J.; Potter, B. V. L. J. Med. Chem. 2005, 48, 5243. |
| [45] | A. Purohit, Woo, L. W. L.; Potter, B. V. L. Cancer Res. 2000, 60, 3394. |
| [46] | Kertesz, N.; Krasnoperov, V.; Reddy, R.; Leshanski, L.; Kumar, S. R.; Zozulya, S.; Gill, P. S. Blood 2006, 107, 2330. |
| [47] | Pasquale, E. B. Nat. Rev. Cancer 2010, 10, 165. |
| [48] | Dohle, W.; Jourdan, F. L.; Menchon, G.; Prota, A. E.; Foster, P. A.; Mannion, P.; Hamel, E.; Thomas, M. P.; Kasprzyk, P. G.; Ferrandis, E.; Steinmetz, M. O.; Leese, M. P.; Potter, B. V. L. J. Med. Chem. 2018, 61, 1031. |
| [49] | Maltais, R.; Djiemeny, A. N.; Roy, J.; Barbeau, X.; Lambert, J.-P.; Poirier, D. Bioorg. Med. Chem. 2020, 28, 115368. |
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