一类苄基咔唑衍生物的合成及其芳香化酶抑制活性
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摘要
许多含咔唑结构的天然产物和药物分子具有广泛的生物和药理活性.在前期研究中发现苄基咔唑类化合物具有芳香化酶抑制活性的基础上,合成10个苄基咔唑衍生物(其中,前7个化合物是未被文献报道过的化合物),采用1H NMR确证它们的结构,在体外酶水平上测定它们对芳香化酶的抑制活性,并总结取代基对其活性影响的构效关系.该研究可为进一步寻找更高活性苄基咔唑类芳香化酶抑制剂提供基础数据和思路.
Many natural substances and drug molecules with the carbazole structure have a broad range of biological and pharmacological activities.Based on our previous discovery that benzyl carbazole possesses aromatase inhibitory activity,ten substitutes were synthesized(the first seven compounds are unreported in literature),and their structure was confirmed by 1H NMR.Their aromatase inhibitory activities were assayed in vitro at enzyme levels and the structure activity relationship was summarized.This research can provide some basic data and ideas for the further search of new benzyl carbazole derivatives with higher aromatase inhibitory activities.
Many natural substances and drug molecules with the carbazole structure have a broad range of biological and pharmacological activities.Based on our previous discovery that benzyl carbazole possesses aromatase inhibitory activity,ten substitutes were synthesized(the first seven compounds are unreported in literature),and their structure was confirmed by 1H NMR.Their aromatase inhibitory activities were assayed in vitro at enzyme levels and the structure activity relationship was summarized.This research can provide some basic data and ideas for the further search of new benzyl carbazole derivatives with higher aromatase inhibitory activities.
引文
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[2]G?uszyńska A.Biological potential of carbazole derivatives[J].European Journal of Medicinal Chemistry,2015,94:405-426.
[3]Hou S,Yi Y W,Kang H J,et al.Novel carbazole inhibits phosphor-STAT3 through induction of protein-tyrosine phosphatase[J].Journal of Medicinal Chemistry,2014,57(15):6342-6353.
[4]Shaikh M S,Karpoormath R,Thapliyal N,et al.Current perspective of natural alkaloid carbazole and its derivatives as antitumor agents[J].Anti-Cancer Agents Medicinal Chemistry,2015,15(8):1049-1065.
[5]Asche C,Demeunynck M.Antitumor carbazoles[J].Anti-Cancer Agents Medicinal Chemistry,2007,7(2):247-267.
[6]Ito C,Itoigawa M,Sato A,et al.Chemical constituents of Glycosmis arborea:Three new carbazole alkaloids and their biological activity[J].Journal of Natual Products,2004,67(9):1488-1491.
[7]Songsiang U,Thongthoom T,Boonyarat C,et al.Claurailas A-D,cytotoxic carbazole alkaloids from the roots of Clausena harmandiana[J].Journal of Natural Products,2011,74(2):208-212.
[8]Dai Y,Xiao Y,Wang Q,et al.Syntheses and QSAR studies of benzylimidazole derivatives and benzylcarbazole as potential aromatase inhibitors[J].Asian Journal of Chemistry,2014,26(8):2381.
[9]Lee C Y,Kuo S C,Teng C M,et al.Synthesis and antiplatelet activity of 9-benzyl-3-(hydroxymethyl)carbazoles[J].Journal of Chinese Pharmaceutical Sciences,2002,54(1):25-34.
[10]Albanese D,Landini D,Penso M,et al.Chemoselective N-alkylation of 2-hydroxycarbazole as a model for the synthesis of N-substituted pyrrole derivatives containing acidic functions[J].Tetrahedron,1995,51(19):5681-5688.
[11]Favia A D,Habrant D,Scarpelli R,et al.Identification and characterization of carprofen as a multitarget fatty acid amide hydrolase/cyclooxygenase inhibitor[J].Journal of Medicinal Chemistry,2012,55(20):8807-8826.
[12]Stresser D M,Turner S D,Mc Namara J,et al.A highthroughput screen to identify inhibitors of aromatase(CYP19)[J].Analytical Biochemistry,2000,284(2):427-430.