新型卤代3-芳基香豆素的合成及其抗癌活性
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摘要
以卤代芳基乙酸和2,3,4-三羟基苯甲醛为主要原料,经Perkin缩合和关环反应制得12个含卤素的7,8-二乙酰氧基-3-芳基香豆素化合物(D_1～D_(12));D_1～D_(12)经水解反应合成了12个含卤素的7,8-二羟基-3-芳基香豆素化合物(E_1～E_(12)),除D_2,D_4～D_6,E_2,E_4～E_6外均为新化合物,其结构经~1H NMR和MS(EI)表征。采用MTT法研究了D_1～E_(12)对人肺癌细胞株(A549)的体外细胞毒性。结果表明:D_1～E_(12)均表现出不同程度的肿瘤细胞增殖抑制活性(IC_(50)≥192.74μmol·L~(-1))。
Twelve halogenated 7,8-diacetoxy-3-arylcoumains(D_1～D_(12)) were prepared by Perkin condensation and cyclization reaction from halogenated aryl acetic acids and 2,3,4-trihydroxybenzaldehyde. Then twelve 7,8-dihydroxyl-3-arylcoumains(E_1～E_(12)) were synthesized by hydrolyzation reaction of D_1～D_(12). All the compounds were novel except D_2, D_4～D_6, E_2 and E_4～E_6. The structures were characterized by ~1H NMR and MS(EI). The in vitro cytotoxicities of compound D_1～E_(12) to human lung cancer cell line(A549) was determined by MTT assay. The results showed that, to some extent, D_1～E_(12) exhibited proliferation inhibitory activities(IC_(50)≥192.74 μmol·L~(-1)).
Twelve halogenated 7,8-diacetoxy-3-arylcoumains(D_1～D_(12)) were prepared by Perkin condensation and cyclization reaction from halogenated aryl acetic acids and 2,3,4-trihydroxybenzaldehyde. Then twelve 7,8-dihydroxyl-3-arylcoumains(E_1～E_(12)) were synthesized by hydrolyzation reaction of D_1～D_(12). All the compounds were novel except D_2, D_4～D_6, E_2 and E_4～E_6. The structures were characterized by ~1H NMR and MS(EI). The in vitro cytotoxicities of compound D_1～E_(12) to human lung cancer cell line(A549) was determined by MTT assay. The results showed that, to some extent, D_1～E_(12) exhibited proliferation inhibitory activities(IC_(50)≥192.74 μmol·L~(-1)).
引文
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[3] MATOS M J, HOGGER V, GASPAR A, et al. Synthesis and adenosine receptors bingding affinities of a series of 3-arylcoumarins[J].J Pharm Pharmacol,2013,65(11):1590-1597.
[4] LIMPER C, WANG Y, RUHL S, et al. Compounds isolated from Paoralea corylifolia seeds inhibit protein kinase activity and induce apoptotic cell death in mammalian cells[J].J Pharm Pharmacol,2013,65(9):1393-1408.
[5] MATOS M J, VILAR S, GARCIA-MORALES V, et al. Insight into the functional and structural properties of 3-arylcoumarin as an interesting scaffold in monoamine oxidase B inhibition[J].Chem Med Chem,2014,9(7):1488-1500.
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[7] MUSA M A, BADISA V L, LATINWO L M, et al. In vitro cytotoxicity of benzopyranone derivatives with basic side chain against human lung cell lines[J].Anticancer Res,2010,30(11):4613-4617.
[8] MUSA M A, BADISA V L, LATINWO L M, et al. Cytotoxic activity of new acetoxycoumarin derivatives in cancer cell lines[J].Anticancer Res,2011,31(6):2017-2022.
[9] MUSA M A, BADISA V L, LATINWO L M, et al. Coumarin-based benzopyranone derivatives induced apoptosis in human lung (A549) cancer cells[J].Anticancer Res,2012,32(10):4271-4276.
[10] MUSA M A, LATINWO L M, VIRGILE C, et al. Synthesis and in vitro evaluation of 3-(4-nitrophenyl)coumarin derivatives in tumor cell lines[J].Bioorg Chem,2015,58:96-103.
[11] MUSA M A, JOSEPH M Y, LATINWO L M, et al. In vitro evaluation of 3-arylcoumarin derivatives in A549 cell line[J].Anticancer Res,2015,35(2):653-659.
[12] 肖春芬,陈辉芳,何笑薇,等. 新型3-芳基香豆素类化合物的合成及抗肿瘤活性研究[J].合成化学,2015,23(5):376-381.
[13] ZHAI X, LI J, HE J, et al. Synthesis and in vitro cytotoxicity of novel 4-disubstituted phthalazimes[J].Chem Lett,2008,19:29-30.
[14] XIAO C F, ZOU Y, DU J L, et al. Hydroxyl substitutional effect on selective synthesis of cis,trans-stilenes and 3-arylcoumarins through Perkin condensation[J].Syn Comm,2012,42:1243-1258.