3-羟基-4-喹诺酮类化合物的设计、合成及其抗增殖活性

王峰华; 王凯; 沈建华; 陈凯先

doi:10.11665/j.issn.1000-5048.20140306

3-羟基-4-喹诺酮类化合物的设计、合成及其抗增殖活性

1.
上海中医药大学中药学院
2.
中科院上海药物研究所新药国家重点实验室

计量
- 文章访问数: 1095
- HTML全文浏览量: 3
- PDF下载量: 1572
出版历程
- 刊出日期: 2014-06-24

Design, synthesis and antiproliferative activity of 3-hydroxy-4-quinolone compounds

摘要

摘要: 将二氢杨梅素和喹诺酮抗肿瘤化合物的结构特征拼合，设计了一系列3-羟基-4-喹诺酮类化合物；以3，5-二甲氧基苯胺为原料，经还原氨化、弗克酰基化、微波促进闭环、BBr₃催化脱甲基、Mannich反应等步骤制备得到16个目标化合物；采用MTT法测定了化合物对肺肿瘤细胞株A549和NCI-H 460的增殖抑制活性。所合成的16个化合物均未见文献报道，其结构经IR、MS、¹H NMR确证；活性测试结果显示，多个化合物对两种细胞株均表现出中等的抗增殖活性，化合物 11b 对NCI-H 46细胞的抑制作用最强。初步构效关系表明:在3-羟基-4-喹诺酮结构的N-1位进入异戊烯基能显著地提高化合物的抗肿瘤活性。
- 3-羟基-4-喹诺酮 /
- 拼合 /
- 合成 /
- 抗肿瘤活性 /
- 构效关系
Abstract: A combination of the structural features of dihydromyricetin and quinolone antineoplastic compounds gave rise to 3-hydroxy-4-quinolone motif. Starting from 3, 5-dimethoxyaniline, the target compounds were prepared through a reaction cascade, including reductive amination, Friedel-Crafts reaction, microwave assisted ring closure, BBr₃ catalyzed demethylation and Mannich reaction. Sixteen novel compounds were synthesized, and their structures were confirmed by IR, MS and ¹H NMR. The antiproliferative activities of the compounds against A549 and NCI-H 460 cells were tested in MTT assay. Several compounds exhibited moderate antiproliferative activities against both cell lines, of which, compound 11b displayed the most robust inhibition towards NCI-H 460. Preliminary structural-activity relationships indicated that introduction of isopentenyl into the N-1 position of 3-hydroxy-4-quinolone motif would significantly improve the potency of the compounds.
- 3-hydroxy-4-quinolone /
- combination /
- synthesis /
- antiproliferative activity /
- structural-activity relationship

HTML全文

参考文献(14)

[1]	Balderas R,Gonzalez BP,Garcia A,et al.Anticancer drug design using scaffolds of β-lactams,sulfonamides,quinoline,quinoxaline and natural products.Drugs advances in clinical trials[J]. Curr Med Chem,2012,19(26):4 377-4 398.
[2]	Liu EH,Qi LW,Wu Q,et al.Anticancer agents derived from natural products[J]. Mini Rev Med Chem,2009,9(13):1 547-1 555.
[3]	Ji WS,Li AL. Medicinal Chemistry(药物化学)[M].Beijing:High Education Press,1999:466-505.
[4]	Zeng S,Liu DU,Ye YL,et al.Anti-tumor efects of ampelopsin on human lung cancer GLC-82 implanted in nude mice[J]. J Chin Med Mate(中药材),2004,27(11):842-845.
[5]	Ohyama M,Tanaka T,Ito T,et al.Antitumor agents 200.Cytotoxicity of naturally occurring resveratrol oligomers and their acetate derivatives[J]. Bio Org Med Chem Lett,1999,9(20):3 057-3 060.
[6]	Liu DY,Luo M.Study on inhibitory effect of ampelopsin on melanoma by serologic pharmacological method[J]. J Chin Med Mate(中药材),2001,24(5):348-350.
[7]	Liu DY,Lei HQ.Inhibitory effects of myricetin and ampelopsin on tyrosinas[J]. Chin Biochem J(生物化学杂志),1996(5):618-620.
[8]	Zhou NN,Zhu XF,Xie BF,et al.Research on the antitumor effects of ampelopsin from Canton Ampelopsis Root[J]. Guangdong Pharm J(广东药学),2000,10(4):7-8.
[9]	Facchinetti V,Gomes CR,de Souza MV,et al.Perspectives on the development of novel potentially active quinolones against tuberculosis and cancer[J]. Mini Rev Med Chem,2012,12(9):866-874.
[10]	Xu QJ,Hou LL,Wu XK,et al.Synthesis and antitumor activity of ciprofloquinolone bis-(C3/C7 hydrazone)s[J].J China Pharm Univ(中国药科大学学报),2013,44(1):35-38.
[11]	Sissi C,Palumbo M.The quinolone family:from antibacterial to anticancer agents[J]. Curr Med Chem Anticancer Agents,2003,3(6):439-450.
[12]	Abbas JA,Stuart RK.Vosaroxin:a novel antineoplastic quinolone[J]. Expert Opin Investig Drugs,2012,21(8):1 223-1 233.
[13]	Chen JC,Huang CS,Liu HX,et al.Prenyl and geranyl favonoids compounds with biological activities[J]. Technol Dev Chem Ind(化工技术与开发),2013,42(1):12-17.
[14]	Sui ZH,Nguyen Van N,Altom J,et al.Synthesis and topoisomerase inhibitory activities of novel aza-analogues of flavones[J]. Eur J Med Chem,1999,34(5):381-387.

施引文献

资源附件(0)

计量

文章访问数: 1095
HTML全文浏览量: 3
PDF下载量: 1572
被引次数: 0

3-羟基-4-喹诺酮类化合物的设计、合成及其抗增殖活性

计量

出版历程

Design, synthesis and antiproliferative activity of 3-hydroxy-4-quinolone compounds

计量

出版历程

目录