广西师范大学学报（自然科学版） ›› 2012, Vol. 30 ›› Issue (1): 60-66.

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苯并菲啶类化合物的合成与生物活性研究

聂岳坤1, 潘成学1, 戴支凯2, 苏桂发1   

  1. 1.广西师范大学化学化工学院药用资源化学与药物分子工程国家重点实验室培育基地,广西桂林541004;
    2.桂林医学院药理实验中心,广西桂林541001
  • 收稿日期:2011-10-28 出版日期:2012-01-20 发布日期:2018-12-03
  • 通讯作者: 潘成学(1974—),男,广西隆安人,广西师范大学副教授,博士。E-mail:panling74@163.com
  • 基金资助:
    广西医药人才小高地科研基金资助项目;教育部重点实验室主任基金资助项目(桂科能07109001-05);广西自然科学基金创新团队资助项目(2010GXNSFF013001)

Synthesis and Bioactivities of Benzo[c]phenanthridine Derivatives

NIE Yue-kun1, PAN Cheng-xue1, DAI Zhi-kai2, SU Gui-fa1   

  1. 1.State Key Laboratory Cultivation Base for the Chemistry andMolecular Engineering of Medicinal Resources,College of Chemistry and Chemical Engineering,Guangxi Normal University,Guilin Guangxi 541004,China;
    2.Pharmacological Experiment Center,Guilin Medical College,Guilin Guangxi541004,China
  • Received:2011-10-28 Online:2012-01-20 Published:2018-12-03

摘要： 以邻甲基苯腈和芳香醛为原料,在强碱催化下经一步反应直接得到11,12-二氢苯并菲啶类化合物,产物再跟3-芳基-3-氯-2-氧丙酸乙酸甲酯反应得到二氢苯并菲啶骈咪唑环化合物,共合成了8个目标化合物,并研究了部分目标产物的抗肿瘤活性及与牛胸腺DNA的相互作用。活性研究结果表明:一些化合物对肝癌(HepG2)、鼻咽癌(CNE)、胃癌(7901)等癌细胞具有较好的体外生长抑制活性,与小牛胸腺DNA具有较强的相互作用。

关键词: 苯并菲啶衍生物, 抗肿瘤, DNA, 咪唑

Abstract: 11,12-Dihydrobenzo[c]phennanthridine derivatives were synthesized starting from aromatic aldehydes and o-methyl benzonitrilein an “one-pot” manner under a strong basic condition.The resulting productscould be further transformed to the benzo[c]phennanthridine-imidazol hybrid by reaction with methyl 3-aryl-3-cholo-2-oxo-propanate,or to benzo[c]phennanthridine derivatives by dehydrogenation to obtain eight target compounds.Their abilities to inhibit the cancer cell lines in vitro and ability tointeract with DNA were studied.The results of the study on bioactivities indicated that some of the compounds had obvious inhibition of certain cell lines andthe ability to interact with DNA.

Key words: benzo[c]phenanthridine derivatives, anti-tumor, DNA, imidazole

中图分类号: 

  • O629.72
[1] TSHIKAWA T.Benzo[c]phenanthridine bases and their antituberculosis activity[J].Med Res Rev,2001,21(1):61-72.
[2] TSUKAMOTO H,KONDO S,MUKUDAI Y,et al.Evaluation of anticancer activities of benzo[c]phenanthridine alkaloid sanguinarine in oral squamous cell carcinoma cell line[J].Anticancer Res,2011,31(9):2841-2846.
[3] VALDERRAMA J A,IBACACHE A,RODRIGUEZ J A,et al.Studies on quinones.Part 47.Synthesis of novel phenylaminophenanthridinequinones as potential antitumor agents[J].Eur J Med Chem,2011,46(8):3398-3409.
[4] YAPI A D,DESBOIS N,CHEZAL J M,et al.Design and preparation of aza-analogues of benzo[c]phenanthridine framework with cytotoxic and antiplasmodial activities[J].Eur J Med Chem,2010,45(7):2854-2859.
[5] IWASAKI H,OKABE T,TAKARA K,et al.Tumor-selective cytotoxicity ofbenzo[c]phenanthridine derivatives from Toddalia asiatica Lam[J].CancerChemotherapy and Pharmacology,2010,65(4):719-726.
[6] 左国营,徐贵丽,赵益斌,等.含有苯并菲啶类生物碱及其衍生物的医药新用途:中国,101084906[P].2007-09-28.
[7] ZHONG Ming,LI Gui-yin,ZENG Jian-guo,et al.Evaluation of molluscicidal activities of benzo[c]phenanthridine alkaloids from Macleaya cordata(Wild) R Br on snail hosts of Schistosoma japonicum[J].J Med Plants Res,2011,5(4):521-526.
[8] LU Pei,HUANG Kang-lun,XIE Long-guan.Palladium-catalyzed tandemreaction to construct benzo[c]phenanthridine:application to the total synthesis of benzo[c]phenanthridine alkaloids[J].Org Biomol Chem,2011,9(9):3133-3135.
[9] ISHIARA Y,AZUMA S,CHOSHI T.Total synthesis of benzo[c]phenanthridine alkaloids based on a microwave-assisted electrocyclic reaction of theaza 6-electron system and structural revision of brousso-npapyrine[J].Tetrahedron,2011,67(6):1320-1333.
[10] KORIVI R P,CHENG Chien-hong.Protecting-group-free total synthesis of isoquinoline alkaloids by nickel-catalyzed annulation of o-halobenzaldimine with an alkyne as the key step[J].Chem Eur J,2010,16(1):282-287.
[11] FISCHER D,TOMEBA T.Iodine-mediated electrophilic cyclization of2-alkynyl-1-methylene azide aromatics leading to highly substituted isoquinolines and its application to the synthesis of norchelerythrine[J].J Am Chem Soc,2008,130(9):15721-15725.
[12] KOCK I,HEBER D,WEIDE M,et al.Synthesis and biological evaluation of 11-substituted 6-aminobenzo[c]phenanthridine derivatives,a new class of antitumor agents[J].J Med Chem,2005,48(8):2772-2777.
[13] FANTINI M,ZULIANI V,RIVARA M,et al.Microwave assisted efficient synthesis of imidazole-based privileged structures[J].J Comb Chem,2010,12(1):181-185.
[14] SEO H J,PARK E J,KIM M J,et al.Design and synthesis of novel arylpiperazine derivatives containingthe imidazole core targeting 5-HT2A receptor and 5-HT transporter[J].J Med Chem,2011,54(18):6305-6318.
[15] WAHAB B A,AWAD G E,BADRIA F A.Synthesis,antimicrobial,antioxidant,anti-hemolytic and cytotoxic evaluation of new imidazole-based heterocycles[J].Eur J Med Chem,2011,46(8):1505-1511.
[16] WANG Le,WOODS K W.Potent,orally active heterocycle-based combretastatin A-4 analogues:synthesis,structu-re-activity relationship,pharmacokinetics,and in vivo antitumor activity evaluation[J].J Med Chem,2002,45(8):1697-1711.
[17] WANG Jian-mei,FERMANDE D R,YANG Yan,et al.Synthesis of oxazolidines using DMSO/P4O10 as a formaldehyde equivalent[J].Tetrahedron:Asymmetry,2007,18(9):1115-1123.
[18] 童裳伦,叶荣民,张全.S2异丙甲草胺与小牛胸腺DNA的相互作用[J].高等学校化学学报,2010,31(5):905-910.
[19] MOSMANN T.Rapid colorimetric assay for cellular growth and survival:application to proliferation and cytotoxicity assays[J].J Immunol Methods,1983,65(1):55-63.
[20] 何华,王羚邮,戴丽,等.测定药物小分子与脱氧核糖核酸相互作用方法的研究进展[J].中国药学杂志,2005,40(7):481-485.
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