Methyl Xestospongoate类似物的设计、合成和抗肿瘤活性

孙冬宇; 龚景旭; 李序文; 韩冠英; 郭跃伟

doi:10.11665/j.issn.1000-5048.20180405

Methyl Xestospongoate类似物的设计、合成和抗肿瘤活性

1.
锦州医科大学药学院
2.
中国科学院上海药物研究所新药研究国家重点实验室
3.
锦州医科大学附属第一医院

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- 刊出日期: 2018-08-24

Studies on methyl xestopongoate analogues:design, synthesis and antitumor activities

摘要

摘要: 设计、合成了52个Methyl Xestospongoate类似物并初步研究了其抗肿瘤活性。以炔基甲酯和二炔为原料，经过Cadiot-Chodkiewitz偶联和Sonogashira偶联反应合成了52个Methyl Xestospongoate类似物 4(a~m) - 7( a ~ m )，并利用¹H NMR、¹³C NMR和HREI-MS法确定其结构，采用CCK-8法测定了部分化合物的体外抗肿瘤活性。结果显示化合物 6k 对A549和P-388肿瘤细胞的增殖具有较强的抑制活性，其IC₅₀分别为9.36和9.62 μmol/L。

关键词:
Methyl Xestospongoate /

聚烯炔 /

类似物 /

合成 /

抗肿瘤活性
Abstract: Fifty-two methyl xestospongoate analogues were designed, synthesized and evaluated for the antiproliferative activity. Starting from alkynyl methyl ester and diyne, methyl xestospongoate analogues 4 ( a - m )- 7( a - m )were synthesized by Cadiot-Chodkiewitz coupling and Sonogashira coupling reactions. Their structures were identified by ¹H NMR, ¹³C NMR and HREI-MS. The cytotoxic inhibiton activities in vitro of some compounds were evaluated against human cancer cells A549 and P-388 by a CCK-8 method. Among them, compound 6k exhibited potent cell growth inhibitory activity against A549 and P-388 cancer cells, with IC₅₀ values of 9. 36 and 9. 62 μmol/L, respectively.

Keywords:
Methyl Xestospongoate /

polyacethlene /

analogues /

synthesis /

antitumor activity

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参考文献(10)

[1] Zhou ZF,Menna M,Cai YS,et al.Polyacetylenes of marine origin:chemistry and bioactivity[J].Chem Rev,2015,115(3):1543-1596.

[2] Martin T,Martin VS.A short synthesis of trans-(+)-laurediol[J].Tetrahedron Lett,2000,41(14):2503-2505.

[3] Hirsh S,Carmely S,Kashman Y.Brominated unsaturated acids from the marine sponge Xestospongia sp.[J].Tetrahedron,1987,43(14):3257-3261.

[4] Taniguchi M,Uchio Y,Yasumoto K,et al.Brominated unsaturated fatty acids from marine sponge collected in Papua New Guinea[J].Chem Pharm Bull,2008,56(3):378-382.

[5] Jiang W,Liu D,Deng ZW,et al.Brominated polyunsaturated lipids and their stereochemistry from the Chinese marine sponge Xestospongia testudinaria[J].Tetrahedron,2011,67(1):58-68.

[6] Morinaka BI,Skepper CK,Molinski TF.Ene-yne tetrahydrofurans from the sponge Xestospongia muta.exploiting a weak CD effect for assignment of configuration[J].Org Lett,2007,9(10):1975-1978.

[7] Bourguet ML,Rakotoarisoa MT,Martin MT,et al.Bioactive bromopolyacetylenes from the marine sponge Xestospongia testudinaria[J].Tetrahedron Lett,1992,33(2):225-226.

[8] Liang LF,Wang T,Cai YS,et al.Brominated polyunsaturated lipids from the Chinese sponge Xestospongia testudinaria as a new class of pancreatic lipase inhibitors[J].E J Med Chem,2014,79(8):290-297.

[9] Gong JX,He WF,Liu HL,et al.Synthesis and evaluation of pancreatic lipase inhibitory effects halogenated polyunsaturated lipids from marine natural products:methyl Xestospongoate and analogs[J].Helv Chim Acta,2016,99(1):78-82.

[10] Gong JX,Wang HY,Yao LG,et al.First Total synthesis of the marine natural brominated polyunsaturated lipid Xestospongenyne as a potent pancreatic lipase inhibitory agent[J].Synlett,2015,27(3):391-394.

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文章访问数: 1231

HTML全文浏览量: 0

PDF下载量: 1234

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刊出日期: 2018-08-24

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[1]	Zhou ZF,Menna M,Cai YS,et al.Polyacetylenes of marine origin:chemistry and bioactivity[J].Chem Rev,2015,115(3):1543-1596.
[2]	Martin T,Martin VS.A short synthesis of trans-(+)-laurediol[J].Tetrahedron Lett,2000,41(14):2503-2505.
[3]	Hirsh S,Carmely S,Kashman Y.Brominated unsaturated acids from the marine sponge Xestospongia sp.[J].Tetrahedron,1987,43(14):3257-3261.
[4]	Taniguchi M,Uchio Y,Yasumoto K,et al.Brominated unsaturated fatty acids from marine sponge collected in Papua New Guinea[J].Chem Pharm Bull,2008,56(3):378-382.
[5]	Jiang W,Liu D,Deng ZW,et al.Brominated polyunsaturated lipids and their stereochemistry from the Chinese marine sponge Xestospongia testudinaria[J].Tetrahedron,2011,67(1):58-68.
[6]	Morinaka BI,Skepper CK,Molinski TF.Ene-yne tetrahydrofurans from the sponge Xestospongia muta.exploiting a weak CD effect for assignment of configuration[J].Org Lett,2007,9(10):1975-1978.
[7]	Bourguet ML,Rakotoarisoa MT,Martin MT,et al.Bioactive bromopolyacetylenes from the marine sponge Xestospongia testudinaria[J].Tetrahedron Lett,1992,33(2):225-226.
[8]	Liang LF,Wang T,Cai YS,et al.Brominated polyunsaturated lipids from the Chinese sponge Xestospongia testudinaria as a new class of pancreatic lipase inhibitors[J].E J Med Chem,2014,79(8):290-297.
[9]	Gong JX,He WF,Liu HL,et al.Synthesis and evaluation of pancreatic lipase inhibitory effects halogenated polyunsaturated lipids from marine natural products:methyl Xestospongoate and analogs[J].Helv Chim Acta,2016,99(1):78-82.
[10]	Gong JX,Wang HY,Yao LG,et al.First Total synthesis of the marine natural brominated polyunsaturated lipid Xestospongenyne as a potent pancreatic lipase inhibitory agent[J].Synlett,2015,27(3):391-394.