当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Antitumor agents. 5. synthesis, structure-activity relationships, and biological evaluation of dimethyl-5H-pyridophenoxazin-5-ones, tetrahydro-5h-benzopyridophenoxazin-5-ones, and 5h-benzopyridophenoxazin-5-ones with potent antiproliferative activity.

Antitumor agents. 5. synthesis, structure-activity relationships, and biological evaluation of dimethyl-5H-pyridophenoxazin-5-ones, tetrahydro-5h-benzopyridophenoxazin-5-ones, and 5h-benzopyridophenoxazin-5-ones with potent antiproliferative activity.

Abstract：

:New antiproliferative compounds, dimethyl-5H-pyrido[3,2-a]phenoxazin-5-ones (1-6), tetrahydro-5H-benzopyrido[2,3-j]phenoxazin-5-ones (7-9), and 5H-benzopyrido[3,2-a]phenoxazin-5-ones (10-12) were synthesized and evaluated against representative human neoplastic cell lines. Dimethyl derivatives 1-6 were more active against carcinoma than leukemia cell lines. The tetrahydrobenzo derivatives 7-9 were scarcely active, whereas the corresponding benzo derivatives 10-12 showed notable cytotoxicity against a majority of the tested cell lines. Molecular modeling studies indicated that the high potency of 10 and 11, the most cytotoxic compounds of the whole series, could be due to the position of the condensed benzene ring, which favors pi-pi stacking interactions with purine and pyrimidine bases in the DNA active site. Biological studies suggested that 10-12 have no effect on human topoisomerases I and II and that they induce arrest at the G2/M phase.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Bolognese A,Correale G,Manfra M,Lavecchia A,Novellino E,Pepe S

doi

10.1021/jm050745l

subject

Has Abstract

pub_date

2006-08-24 00:00:00

pages

5110-8

issue

17

eissn

0022-2623

issn

1520-4804

journal_volume

49

pub_type

杂志文章

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