当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Discovery and investigation of antiproliferative and apoptosis-inducing properties of new heterocyclic podophyllotoxin analogues accessible by a one-step multicomponent synthesis.

Discovery and investigation of antiproliferative and apoptosis-inducing properties of new heterocyclic podophyllotoxin analogues accessible by a one-step multicomponent synthesis.

Abstract：

:Podophyllotoxin has been extensively used as a lead agent in the development of new anticancer drugs. On the basis of the previously reported simplified 4-aza-2,3-didehydro podophyllotoxin analogues, we implemented a bioisosteric replacement of the methylenedioxybenzene subunit with a pyrazole moiety to afford tetracyclic dihydropyridopyrazoles. Libraries of these structurally simple analogues are prepared by a straightforward one-step multicomponent synthesis and demonstrated to display antiproliferative properties in a number of human cancer cell lines. These new heterocycles potently induce apoptosis in cancerous Jurkat cells even after a short 24 h exposure. In contrast, no apoptosis is detected in primary lymphocytes under the same treatment conditions. The ease of synthesis and encouraging biological activities make the presented library of dihydropyridopyrazoles promising new leads in anticancer drug design.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Magedov IV,Manpadi M,Slambrouck SV,Steelant WF,Rozhkova E,Przheval'skii NM,Rogelj S,Kornienko A

doi

10.1021/jm070528f

subject

Has Abstract

pub_date

2007-10-18 00:00:00

pages

5183-92

issue

21

eissn

0022-2623

issn

1520-4804

journal_volume

50

pub_type

杂志文章

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