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Potential antitumor agents. 49. 5-substituted derivatives of N-[2-(dimethylamino)ethyl]-9-aminoacridine-4-carboxamide with in vivo solid-tumor activity.

Abstract：

:Derivatives of N-[2-(dimethylamino)ethyl]-9-aminoacridine-4-carboxamide bearing a wide variety of different groups at the 5-position (and for comparative purposes at the 7-position) have been prepared, and their physicochemical properties and biological activities have been determined. Although both 5- and 7-substituted compounds bind equally well to DNA by intercalation, only the 5-substituted compounds have in vivo antitumor activity. All the 5-substituted compounds showed in vivo antileukemic activity, but only those bearing electron-withdrawing substituents sufficiently powerful to ensure the acridine chromophore was uncharged at physiological pH showed activity in vivo against the Lewis lung solid tumor. The weakly basic derivatives do not show greater intrinsic cytotoxicity or selectivity toward solid tumor cells, and their broader spectrum of in vivo antitumor activity is attributed to the fact that they exist predominantly as monocations, which can distribute more efficiently.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Denny WA,Atwell GJ,Rewcastle GW,Baguley BC

doi

10.1021/jm00387a013

subject

Has Abstract

pub_date

1987-04-01 00:00:00

pages

658-63

issue

4

eissn

0022-2623

issn

1520-4804

journal_volume

30

pub_type

杂志文章

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