Chinese Journal of Organic Chemistry >
Synthesis and Evaluation in vitro of Novel Harmine Derivatives as Anticancer Activity Agents
Received date: 2021-12-07
Revised date: 2022-02-12
Online published: 2022-02-25
Supported by
Sichuan Provincial Administration of Traditional Chinese Medicine Technology Plan(2020JC0069); Science and Technology Plan of Leshan(20SZD067); Science and Technology Plan of Leshan(20NZD007); Research Foundation of Leshan Vocational & Technical College(KY2019015); Research Foundation of Leshan Vocational & Technical College(KY2019016)
A series of novel 6-substituted harmine derivatives were synthesized from harmine in five steps: N9-methylation, bromination, Suzuki coupling, N-Boc deprotection, and amidation reaction. The structures of target compounds were confirmed by 1H NMR, 13C NMR, and high-resolution mass spectra (HRMS). The in vitro antiproliferative activities were evaluated in a panel of cancer cell lines (HL-60, A549, SMMC-7721, MCF-7 and SW-480) via 3-(4,5-dimethylthiazol-2-yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. The results indicated that some compounds had good to excellent activities, and especially the most potent compound was 3o, whose IC50 values were 0.27 (against HL-60), 0.44 (against A549) and 0.048 μmol/L (against SMMC-7721), better than positive control drugs cisplatin and taxol (against SMMC-7721).
Key words： harmine; derivatization; antitumor activity
Dongyan Hu , Guangtian Han , Xi'an Li , Huazhong Ren , Lirong Yue , Li Guo , Jiafu Feng . Synthesis and Evaluation in vitro of Novel Harmine Derivatives as Anticancer Activity Agents[J]. Chinese Journal of Organic Chemistry, 2022 , 42(6) : 1863 -1871 . DOI: 10.6023/cjoc202112015
| [1] | Cortes, J.; Perez-Garcia, J. M.; Llombart-Cussac, A.; Curigliano, G.; El Saghir, N. S.; Cardoso, F.; Barrios, C. H.; Javier Roman, Sh. W. M.; Harbeck, N.; Eniu, A.; Kaufman, P. A.; Tabernero, J.; García-Estévez, L.; Frcp, P. S.; Arribas, J. CA-Cancer J. Clin. 2020, 70, 105. |
| [2] | Ali, I.; Wani, W. A.; Saleem, K.; Haque, A. Anticancer Agents Med. Chem. 2013, 13, 296. |
| [3] | (a) Wiseman. M. P. Nutr. Soc. 2008, 67, 253. |
| [3] | (b) Leite de Oliveira, R.; Deschoemaeker, S; Henze, A.-T.; Debackere, K.; Finisguerra, V.; Takeda, Y.; Roncal, C.; Dettori, D.; Tack, E.; Jönsson, Y. Cancer Cell 2012, 22, 263. |
| [4] | Edwankar, C. R.; Edwankar, R. V.; Namjoshi, O. A.; Rallapalli, S. K.; Yang, J.; Cook, J. M. Curr. Opin. Drug Discovery Dev. 2009, 12, 752. |
| [5] | Chen, Q.; Chao, R. H.; Chen, H. S.; Hou, X. R.; Yan, H. F.; Zhou, S. F.; Peng, W. L.; Xu, A. L. Int. J. Cancer. 2005, 114, 675. |
| [6] | Shankaraiah, N.; Siraj, K. P.; Nekkanti, S.; Srinivasulu, V.; Sharma, P.; Senwar, K. R.; Sathish, M.; Vishnuvardhan, M. V. P. S.; Ramakrishna, S.; Jadala, C.; Nagesh, N.; Kamal, A. Bioorg. Chem. 2015, 59, 130. |
| [7] | Jenkins, P. R.; Wilson, J.; Emmerson, D.; Garcia, M. D.; Smith, M. R.; Gray, S. J.; Britton, R. G.; Mahale, S.; Chaudhuri, B. Bioorg. Med. Chem. 2008, 16, 7728. |
| [8] | Han, X. M.; Zhang, J.; Guo, L.; Cao, R. H.; Li, Y. Z.; Li, N; Ma, Q.; Wu, J. L.; Wang, Y. C.; Si, S. Y. PLoS One 2012, 7, e46546. |
| [9] | Figueiredo, P. D.; Perdomo, R. T.; Garcez, F. R.; Matos, M. D. C.; Carvalho, J. E.; Garcez, W. S. Bioorg. Med. Chem. Lett. 2014, 24, 1358. |
| [10] | Trujillo, J. I.; Meyers, M. J.; Anderson, D. R.; Hegde, S.; Mahoney, M. W.; Vernier, W. F.; Buchler, I. P.; Wu, K. K.; Yang, S.; Hartmann, S. J.; Reitz, D. B. Bioorg. Med. Chem. Lett. 2009, 19, 2365. |
| [11] | Xin, B. T.; Tang, W. F.; Wang, Y.; Lin, G. W.; Liu, H. C.; Jiao, Y.; Zhu, Y.; Yuan, H. L.; Chen, Y. D.; Lu, T. Bioorg. Med. Chem. Lett. 2012, 22, 4783. |
| [12] | Du, H. T.; Gu, H. L.; Li, N.; Wang, J. R. Med. Chem. Commun. 2016, 7, 636. |
| [13] | (a) Insaf, F.; Jalloul, B.; Mansour, Z.; Fatima, B. E. G.; Hichem, B. J. J. Enzyme Inhib. Med. Chem. 2015, 30, 371. |
| [13] | (b) Insaf, F.; Mohamed, A. B.; Aymen, B. N.; Jean, P. S.; Hichem, B. J.; Jalloul, B. J. Enzyme Inhib. Med. Chem. 2016, 31, 23. |
| [14] | Shi, B. X.; Cao, R. H.; Fan, W. X.; Guo, L.; Ma, Q.; Chen, X. M.; Zhang, G. X.; Qiu, L. Q.; Song, H. C. Eur. J. Med. Chem. 2013, 60, 10. |
| [15] | Cao, R. H.; Fan, W. X.; Guo, L.; Ma, Q.; Zhang, G. X.; Li, J. R.; Chen, X. M.; Ren, Z. H.; Qiu, L. Q. Eur. J. Med. Chem. 2013, 60, 135. |
| [16] | Sun, Y.; Guo, L.; Fan, W. X.; Chen, W.; Zhang, J.; Dai, B. Chin. J. Org. Chem. 2021, 41, 400. (in Chinese) |
| [16] | ( 孙跃, 郭亮, 范文玺, 陈伟, 张洁, 代斌, 有机化学, 2021, 41, 400.) |
| [17] | Cao, R. H.; Chen, Q.; Hou, X. R.; Chen, H. S.; Guan, H. J.; Ma, Y.; Peng, W. L.; Xu, A. L. Bioorg. Med. Chem. 2004, 12, 4613. |
/
| 〈 |
|
〉 |
