通过一步多组分合成可获得的吡喃并[3,2-c]吡啶酮的抗增殖和诱导凋亡特性。
Antiproliferative and apoptosis inducing properties of pyrano[3,2-c]pyridones accessible by a one-step multicomponent synthesis.
作者信息
Magedov Igor V, Manpadi Madhuri, Evdokimov Nikolai M, Elias Eerik M, Rozhkova Elena, Ogasawara Marcia A, Bettale Jennifer D, Przheval'skii Nikolai M, Rogelj Snezna, Kornienko Alexander
机构信息
Department of Organic Chemistry, Timiryazev Agriculture Academy, Moscow 127550, Russia.
出版信息
Bioorg Med Chem Lett. 2007 Jul 15;17(14):3872-6. doi: 10.1016/j.bmcl.2007.05.004. Epub 2007 May 6.
Abstract
4-Arylpyrano-[3,2-c]-pyridones have been prepared by a one-step cyclocondensation of 4-hydroxy-1,6-dimethylpyridin-2(1H)-one with various substituted benzaldehydes and malononitrile. These heterocycles exhibit micromolar and submicromolar antiproliferative activity in HeLa and induce apoptosis in Jurkat cell lines. Structure-activity studies performed on a small library of these compounds show a pronounced cytotoxicity enhancing effect of the bromo substituent at the meta position of the C4 aromatic moiety.
摘要
通过4-羟基-1,6-二甲基吡啶-2(1H)-酮与各种取代苯甲醛和丙二腈的一步环缩合反应制备了4-芳基吡喃并-[3,2-c]-吡啶酮。这些杂环化合物在HeLa细胞中表现出微摩尔和亚微摩尔级别的抗增殖活性，并在Jurkat细胞系中诱导细胞凋亡。对这些化合物的一个小文库进行的构效关系研究表明，C4芳基部分间位的溴取代基具有显著的细胞毒性增强作用。
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本文引用的文献
1
Antineoplastic Agents. 554. The manitoba bacterium Streptomyces sp.
J Nat Prod. 2006 May;69(5):804-6. doi: 10.1021/np058087v.
2
Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 2. Structure-activity relationships of the 7- and 5-, 6-, 8-positions.
Bioorg Med Chem Lett. 2005 Nov 1;15(21):4745-51. doi: 10.1016/j.bmcl.2005.07.066.
3
Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 1. Structure-activity relationships of the 4-aryl group.
J Med Chem. 2004 Dec 2;47(25):6299-310. doi: 10.1021/jm049640t.
4
Antivascular and antitumor evaluation of 2-amino-4-(3-bromo-4,5-dimethoxy-phenyl)-3-cyano-4H-chromenes, a novel series of anticancer agents.
Mol Cancer Ther. 2004 Nov;3(11):1375-84.
5
Discovery and mechanism of action of a novel series of apoptosis inducers with potential vascular targeting activity.
Mol Cancer Ther. 2004 Nov;3(11):1365-74.
6
A short-term clinical evaluation of L-697,661, a non-nucleoside inhibitor of HIV-1 reverse transcriptase. L-697,661 Working Group.
N Engl J Med. 1993 Oct 7;329(15):1065-72. doi: 10.1056/NEJM199310073291502.
7
Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.
J Immunol Methods. 1983 Dec 16;65(1-2):55-63. doi: 10.1016/0022-1759(83)90303-4.
8
Milrinone, a new agent for the treatment of congestive heart failure.
Clin Pharm. 1986 Mar;5(3):201-5.
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