A new method of preparation for natural product Uncinine was reported. According to the method, a series of novel butenolides derivatives were designed and synthesized based on the natural product Uncinine. Most of the synthetic compounds showed significant anti proliferation activity against MGC-803. Among of them, (Z)-5-(4-(tert-butyl)-benzylidene)-3-(morpholinomethyl)furan-2(5H)-one (9l) showed potent anticancer effect with IC50 of 2.9 μmol/L in gastric cancer cell MGC803 and showed good selectivity to gastric cancer cells MGC803, HGC27, SGC7901 and less cytotoxicity in normal gastric epithelial cell line (GES1). The research on the molecular level suggests that the mechanism of compound 9l inducing apoptosis in gastric cancer cells is partially dependent on activation of caspase-9/3.
Xu Haiwei
,
Li Yuanyuan
,
Dong Hangqi
,
Meng Xia
,
Zhao Lingjie
,
Lü Chuntao
,
Wang Zhenya
,
Jin Chengyun
. Design and Synthesis of Novel Butenolide Derivatives and Inducing Apoptosis in Gastric Cancer Cells[J]. Chinese Journal of Organic Chemistry, 2020
, 40(1)
: 69
-77
.
DOI: 10.6023/cjoc201907018
[1] Manchoju, A.; Annadate, R. A.; Desquien, L.; Pansare, S. V. Org. Biomol. Chem. 2018, 16, 6224.
[2] Fáková, H.; Pour, M.; Kuneš, J.; Šenel, P. Tetrahedron Lett. 2005, 46, 8137.
[3] David, S.; Peter, B.; Andreas, R.; Wilhelm, S. Toxicol. Lett. 2018, 295, 369.
[4] Dasmahapatra, G.; Lembersky, D.; Son, M. P.; Patel, H.; Peterson, D.; Attkisson, E.; Fisher, R. I.; Friedberg, J. W.; Dent, P.; Grant, S. Mol. Cancer Ther. 2019, 18, 1180.
[5] Germain, A. D. S.; Clavé, G.; Badetdenisot, M. A.; Pillot, J. P.; Cornu, D. Nat. Chem. Biol. 2016, 12, 1552.
[6] Xu, H. W.; Zhao, L. J.; Liu, H. F.; Zhao, D.; Luo, J.; Xie, X. P.; Liu, W. S.; Zheng, J. X.; Dai, G. F.; Liu, H. M.; Liu, L. H.; Liang, Y. B. Bioorg. Med. Chem. Lett. 2014, 24, 2388.
[7] Xu, H.W.; Jia, S. L.; Xie, X. P.; Luo, J.; Wang, S. H. Chin. J. Org. Chem. 2017, 37, 902(in Chinese). (徐海伟, 贾世龙, 谢晓平, 罗姣, 王树, 有机化学, 2017, 37, 902.)
[8] Necula, L.; Matei, L.; Dragu, D.; Neagu, A. I.; Mambet, C.; Nedeianu, S.; Bleotu, C.; Diaconu, C. C.; Chivu-Economescu, M. World J. Gastroenterol. 2019, 17, 2029.
[9] Xu, H. W.; Liu, G. Z.; Zhu, S. L.; Hong, G. F.; Liu, H. M.; Wu, Q. Steroids 2010, 75, 419.
[10] Xu, H. W.; Wang, J. F.; Liu, G. Z.; Hong, G. F.; Liu, H. M. Org. Biomol. Chem. 2007, 5, 1247.
[11] Caroppi, P.; Sinibaldi, F.; Fiorucci, L.; Santucci, R. Curr. Med. Chem. 2009, 16, 4058.
[12] Fulda, S.; Debatin, K. M. Oncogene 2006, 25, 4798.
[13] Danial, N. N.; Korsmeyer, S. J. Cell 2004, 116, 205.
[14] Fulda,S.; Debatin, K. M. Eur. J. Cancer 2005, 41, 786.
[15] Cui, Q; Wang, J. A.; Yang, H. S.; Xie, L. G. Chin. J. Org. Chem. 2010, 30, 1705(in Chinese). (崔庆, 王娇, 杨海申, 谢龙观, 徐效华, 有机化学, 2010, 30, 1705.)
