Citation: Ying Meng, Guan Wang, Yue Li, Kuan Hou, Yue Yuan, Li-Juan Zhang, Hong-Rui Song, Wei Shi. Synthesis and biological evaluation of new pyrrolopyrazinone compounds as potential antitumor agents[J]. Chinese Chemical Letters, ;2013, 24(07): 619-621. shu

Synthesis and biological evaluation of new pyrrolopyrazinone compounds as potential antitumor agents

Ying Meng ^a ,
Guan Wang ^b ,
Yue Li ^a ,
Kuan Hou ^a ,
Yue Yuan ^a ,
Li-Juan Zhang ^a ,
Hong-Rui Song ^a,, ,
Wei Shi ^b,,

1.
a Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China;
2.
b Key Laboratory for Molecular Enzymology and Engineering, Ministry of Education, Jilin University, Changchun 130012, China

Corresponding author: Hong-Rui Song, Wei Shi,
Received Date: 6 March 2013
Available Online: 28 March 2013

A series of pyrrolo[1,2-a]pyrazinone compounds (5a-9f) were synthesized, and their cytotoxic activity against SKOV-3, A549, HeLa cells in vitro were evaluated by the MTT method. Some of the compounds showed potential antitumor activity against three tumor cell lines. Among them, compounds 9c and 9d showed the most potent cytotoxic activity. The preliminary mechanism of action was discussed.
- Pyrrolopyrazinone,
- Antitumor,
- Synthesis
1. [1]
  [1] F. Deng, J.J. Lu, H.Y. Liu, Synthesis and antitumor activity of novel salvicine analogues, Chin. Chem. Lett. 22 (2011) 25-28.
2. [2]
  [2] E.N. Delphine, M. Peter, L. Thomas, Chiroptical analysis of marine sponge alkaloids sharing the pyrrolopyrazinone core, Chem. Eur. J. 10 (2004) 1141-1148.
3. [3]
  [3] A. Umeyama, S. Ito, E. Yuasa, et al., A new bromopyrrole alkaloid and the optical resolution of the racemate from the marine sponge Homaxinella sp., J. Nat. Prod. 61 (1998) 1433-1434.
4. [4]
  [4] G.B. Martin, M.B. Andrew, C.W. Anthony, First syntheses of the pyrroloketopiperazine marine natural products (±)-longamide, (±)-longamide B, (±)-longamide B methyl ester and (±)-hanishin, New J. Chem. 23 (1999) 687-690.
5. [5]
  [5] R.B. Kinnel, H.P. Gehrken, R. Swali, Palau'amine and its congeners: a family of bioactive bisguanidines from the marine sponge Stylotella aurantium 1, J. Org. Chem. 63 (1998) 3281-3286.
6. [6]
  [6] L. Thomas, J.E.N. Delphine, Z. Michael, Study on the absolute configuration of ()-palau'amine, Tetrahedron Lett. 51 (2010) 6353-6355.
7. [7]
  [7] Data for new compounds. 5a: Yield 62%. Mp: 147-150℃; ESI-MS: m/z 163.9[M+H]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 6.95 (s, 1H), 6.63 (d, 1H), 6.19-6.12 (m, 1H), 4.83 (s, 1H), 4.67 (s, 2H), 1.13 (s, 3H). 5b: Yield 67%. Mp: 153-155℃; ESI-MS: m/z 192.2 [M+H]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 6.99-6.93 (m, 1H), 6.60 (dd, 1H), 6.13 (dd, 1H), 4.24 (d, 1H), 3.89 (d, 1H), 3.51 (dt, 1H), 3.36-3.24 (m, 2H), 3.13 (m, 2H), 1.17 (s, 3H). 6a: Yield 31%. Mp: 144-146℃; ESI-MS: m/z 205.9 [M+H]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 7.32 (dd, 1H), 7.24 (s, 1H), 6.83-6.80 (m, 1H), 6.50 (dd, 1H), 5.37 (s, 1H), 2.20 (s, 3H), 1.13 (s, 3H). 6b: Yield 27%. Mp: 182-185℃; ESIMS: m/z 234.2 [M+H]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 7.33 (m, 1H), 7.25 (dd, 1H), 6.84 (dd, 1H), 6.50 (s, 1H), 4.06 (m, 2H), 3.50 (m, 2H), 2.24 (s, 3H), 1.23 (s, 3H). 6c: Yield 36%. Mp: 176-178℃; ESI-MS: m/z 261.9 [M+Na]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 7.33 (dd, 1H), 7.24 (s, 1H), 6.84-6.79 (m, 1H), 6.50 (dd, 1H), 5.39 (s, 2H), 2.21 (s, 3H). 6d: Yield 34%. Mp: 200-202℃; ESI-MS: m/z 267.9 [M+H]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 7.11-7.05 (m, 1H), 6.66 (dd, 1H), 6.14 (dd, 1H), 4.94 (d, 1H), 4.94 (d, 1H), 4.51-4.29 (m, 1H), 4.07 (dt, 1H), 3.99 (d, 1H), 3.95-3.78 (m, 1H), 3.73 (dd, 1H), 3.45 (dt, 1H), 1.40 (s, 3H). 8a: Yield 73%. Mp: 139-141℃; ESIMS: m/z 240 [M]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 7.44 (d, J=8.2 Hz, 1H), 7.09 (s, 1H), 7.03 (d, J=8.2 Hz, 2H), 6.66 (d, 1H), 6.55 (s, 1H), 5.93-5.88 (m, 1H), 5.50 (s, 2H), 2.20 (s, 3H). 8b: Yield 78%. Mp: 191-193℃; ESI-MS: m/z 268 [M]⁺, ¹H NMR (300 MHz, DMSO-d₆): δ 7.11 (d, 2H, J=8.2 Hz), 7.03 (d, 2H, J=8.2 Hz), 6.72-6.67 (m, 1H), 6.56 (dd, 1H), 5.97 (dd, 1H), 4.55 (d, 1H), 4.30 (t, 1H), 4.23 (d, 1H), 3.54 (dt, 1H), 3.47-3.35 (m, 1H), 2.18 (s, 3H), 1.02 (t, 2H). 9a: Yield 29%. Mp: 111-112℃; ESI-MS: m/z 282 [M+H]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 10.52 (s, 1H), 7.45 (dd, 1H), 7.37 (s, 1H), 7.27 (d, 2H, J=8.1 Hz), 7.19 (d, 2H, J=8.1 Hz), 6.96 (d, 1H, J=3.9 Hz), 6.57 (dd, 1H, J=3.9, 2.6 Hz), 2.31 (s, 3H), 1.71 (s, 3H). 9b: Yield 31%. Mp: 194-197℃; ESI-MS: m/z 310 [M+H]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 7.18 (d, 2H, J=8.3 Hz), 7.13-7.09 (m, 1H), 7.06 (d, 2H, J=8.3 Hz), 6.60 (dd, 1H), 6.09 (dd, 1H), 5.62 (d, 1H, J=13.0 Hz), 4.34 (d, 1H, J=13.0 Hz), 4.22-4.10 (m, 1H), 3.94 (dd, 1H), 3.88-3.77 (m, 1H), 3.62 (dt, 1H), 2.21 (s, 3H), 2.04 (s, 3H). 9c: Yield 23%. Mp: 110-113℃; ESI-MS: m/z 316 [M+H]⁺; ¹H NMR(300 MHz, DMSO-d₆): δ 7.90 (d, 2H, J=8.2 Hz), 7.35 (d, 2H, J=8.2 Hz), 7.13-7.08 (m, 1H), 6.87 (dd, 1H), 6.14 (dd, 1H), 5.81 (s, 2H), 3.57 (s, 2H), 2.37 (s, 3H). 9d: Yield 23%. Mp: 191-193℃; ESI-MS: m/z 343.9 [M+H]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 7.15 (d, 2H, J=8.3 Hz), 7.12-7.09 (m, 1H), 7.05 (d, 2H, J=8.3 Hz), 6.59 (dd, 1H), 6.07 (dd, 1H), 5.60 (d, 1H), 4.40 (dt, 3H), 4.16 (dt, 1H), 4.03-3.80 (m, 2H), 3.62 (dt, 1H), 2.18 (s, 3H). 9e: Yield 32%. Mp: 123-125℃; ESI-MS: m/z 330 [M+H]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 10.71 (s, 1H), 7.49-7.33 (m, 2H), 7.25 (d, 2H, J=7.9 Hz), 7.17 (d, 2H, J=7.9 Hz), 6.97 (s, 1H), 6.57 (s, 1H), 3.57 (t, 2H), 2.70-2.52 (m, 2H), 2.28 (s, 3H). 9f: Yield 27%. Mp: 192-194℃; ESI-MS: m/z 357.5 [M+H]⁺, 380 [M+Na]⁺; ¹H NMR (300 MHz, DMSOd₆): δ 7.18 (d, 2H, J=8.3 Hz), 7.12 (d, 1H), 7.04 (d, 2H, J=8.3 Hz), 6.71-6.51 (m, 2H), 6.26-6.00 (m, 2H), 5.82-5.52 (m, 2H), 4.33 (m, 1H), 4.22-4.09 (m, 1H), 4.04 (m, 1H), 3.99-3.89 (m, 1H), 3.73 (dt, 1H), 3.68-3.54 (m, 1H), 2.18 (s, 3H).
1. [1]
  Huijie An , Chen Yang , Zhihui Jiang , Junjie Yuan , Zhongming Qiu , Longhao Chen , Xin Chen , Mutu Huang , Linlang Huang , Hongju Lin , Biao Cheng , Hongjiang Liu , Zhiqiang Yu . Luminescence-activated Pt(Ⅳ) prodrug for in situ triggerable cancer therapy. Chinese Chemical Letters, 2024, 35(7): 109134-. doi: 10.1016/j.cclet.2023.109134
2. [2]
  Yulong Shi , Fenbei Chen , Mengyuan Wu , Xin Zhang , Runze Meng , Kun Wang , Yan Wang , Yuheng Mei , Qionglu Duan , Yinghong Li , Rongmei Gao , Yuhuan Li , Hongbin Deng , Jiandong Jiang , Yanxiang Wang , Danqing Song . Chemical construction and anti-HCoV-OC43 evaluation of novel 10,12-disubstituted aloperine derivatives as dual cofactor inhibitors of TMPRSS2 and SR-B1. Chinese Chemical Letters, 2024, 35(5): 108792-. doi: 10.1016/j.cclet.2023.108792
3. [3]
  Hong-Tao Ji , Yu-Han Lu , Yan-Ting Liu , Yu-Lin Huang , Jiang-Feng Tian , Feng Liu , Yan-Yan Zeng , Hai-Yan Yang , Yong-Hong Zhang , Wei-Min He . Nd@C₃N₄-photoredox/chlorine dual catalyzed synthesis and evaluation of antitumor activities of 4-alkylated sulfonyl ketimines. Chinese Chemical Letters, 2025, 36(2): 110568-. doi: 10.1016/j.cclet.2024.110568
4. [4]
  Jiaming Xu , Yu Xiang , Weisheng Lin , Zhiwei Miao . Research Progress in the Synthesis of Cyclic Organic Compounds Using Bimetallic Relay Catalytic Strategies. University Chemistry, 2024, 39(3): 239-257. doi: 10.3866/PKU.DXHX202309093
5. [5]
  Jing Zhang , Charles Wang , Yaoyao Zhang , Haining Xia , Yujuan Wang , Kun Ma , Junfeng Wang . Application of magnetotactic bacteria as engineering microrobots: Higher delivery efficiency of antitumor medicine. Chinese Chemical Letters, 2024, 35(10): 109420-. doi: 10.1016/j.cclet.2023.109420
6. [6]
  Jin Wang , Xiaoyan Pan , Junyu Zhang , Qingqing Zhang , Yanchen Li , Weiwei Guo , Jie Zhang . Active molecule-based theranostic agents for tumor vasculature normalization and antitumor efficacy. Chinese Chemical Letters, 2024, 35(8): 109187-. doi: 10.1016/j.cclet.2023.109187
7. [7]
  Zhaomin Tang , Qian He , Jianren Zhou , Shuang Yan , Li Jiang , Yudong Wang , Chenxing Yao , Huangzhao Wei , Keda Yang , Jiajia Wang . Active-transporting of charge-reversal Cu(Ⅱ)-doped mesoporous silica nanoagents for antitumor chemo/chemodynamic therapy. Chinese Chemical Letters, 2024, 35(7): 109742-. doi: 10.1016/j.cclet.2024.109742
8. [8]
  Huimin Luan , Qinming Wu , Jianping Wu , Xiangju Meng , Feng-Shou Xiao . Templates for the synthesis of zeolites. Chinese Journal of Structural Chemistry, 2024, 43(4): 100252-100252. doi: 10.1016/j.cjsc.2024.100252
9. [9]
  Zhaojun Liu , Zerui Mu , Chuanbo Gao . Alloy nanocrystals: Synthesis paradigms and implications. Chinese Journal of Structural Chemistry, 2023, 42(11): 100156-100156. doi: 10.1016/j.cjsc.2023.100156
10. [10]
  Zhenhao Wang , Yuliang Tang , Ruyu Li , Shuai Tian , Yu Tang , Dehai Li . Bioinspired synthesis of cochlearol B and ganocin A. Chinese Chemical Letters, 2024, 35(7): 109247-. doi: 10.1016/j.cclet.2023.109247
11. [11]
  Hui Jin , Qin Cai , Peiwen Liu , Yan Chen , Derong Wang , Weiping Zhu , Yufang Xu , Xuhong Qian . Multistep continuous flow synthesis of Erlotinib. Chinese Chemical Letters, 2024, 35(4): 108721-. doi: 10.1016/j.cclet.2023.108721
12. [12]
  Caihong Mao , Yanfeng He , Xiaohan Wang , Yan Cai , Xiaobo Hu . Synthesis and molecular recognition characteristics of a tetrapodal benzene cage. Chinese Chemical Letters, 2024, 35(8): 109362-. doi: 10.1016/j.cclet.2023.109362
13. [13]
  Mei Peng , Wei-Min He . Photochemical synthesis and group transfer reactions of azoxy compounds. Chinese Chemical Letters, 2024, 35(8): 109899-. doi: 10.1016/j.cclet.2024.109899
14. [14]
  Liyong Ding , Zhenhua Pan , Qian Wang . 2D photocatalysts for hydrogen peroxide synthesis. Chinese Chemical Letters, 2024, 35(12): 110125-. doi: 10.1016/j.cclet.2024.110125
15. [15]
  Xiaoyu Chen , Jiahao Hu , Jingyi Lin , Haiyang Huang , Changqing Ye , Hongli Bao . Biisoindolylidene solvatochromic fluorophores: Synthesis and photophysical properties. Chinese Chemical Letters, 2025, 36(2): 109923-. doi: 10.1016/j.cclet.2024.109923
16. [16]
  Tengfei Xuan , Xinyu Zhang , Wei Han , Yidong Huang , Weiwu Ren . Total synthesis of (+)-taberdicatine B and (+)-tabernabovine B. Chinese Chemical Letters, 2025, 36(2): 109816-. doi: 10.1016/j.cclet.2024.109816
17. [17]
  Yuqing Liu , Yu Yang , Yuhan E , Changlong Pang , Di Cui , Ang Li . Insight into microbial synthesis of metal nanomaterials and their environmental applications: Exploration for enhanced controllable synthesis. Chinese Chemical Letters, 2024, 35(11): 109651-. doi: 10.1016/j.cclet.2024.109651
18. [18]
  Wenyi Mei , Lijuan Xie , Xiaodong Zhang , Cunjian Shi , Fengzhi Wang , Qiqi Fu , Zhenjiang Zhao , Honglin Li , Yufang Xu , Zhuo Chen . Design, synthesis and biological evaluation of fluorescent derivatives of ursolic acid in living cells. Chinese Chemical Letters, 2024, 35(5): 108825-. doi: 10.1016/j.cclet.2023.108825
19. [19]
  Shengkai Li , Yuqin Zou , Chen Chen , Shuangyin Wang , Zhao-Qing Liu . Defect engineered electrocatalysts for C–N coupling reactions toward urea synthesis. Chinese Chemical Letters, 2024, 35(8): 109147-. doi: 10.1016/j.cclet.2023.109147
20. [20]
  Uttam Pandurang Patil . Porous carbon catalysis in sustainable synthesis of functional heterocycles: An overview. Chinese Chemical Letters, 2024, 35(8): 109472-. doi: 10.1016/j.cclet.2023.109472

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(604)
HTML views(3)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142