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Bis(bioreductive) alkylating agents: synthesis and biological activity in a nude mouse human carcinoma model.

Abstract：

:Chemical investigations leading to the construction of bis(bioreductive) alkylating agents having both conformationally restricted and mobile spacer regions are described. Two targets having the conformationally mobile ethylene spacer group, namely, 2,2'-ethylenebis[6-(hydroxymethyl)-p-benzoquinone] diacetate (3b) and 2,2'-ethylenebis[6-(bromomethyl)-p-benzoquinone] (3c), were studied in vivo and in vitro using an established epithelial/Burkitt lymphoma hybrid cell line (D98/HR1) previously shown to induce carcinomas in nude mice. Inactivity of both test compounds in vitro, the relative resistance of these cells to test drugs in vitro, and the selective antitumor properties of the bis(bromomethyl) analogue in vivo lead to the proposal that this compound undergoes bioreduction to an alkylating species in the hypoxic core of the tumor, thereby exerting its action.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Witiak DT,Kamat PL,Allison DL,Liebowitz SM,Glaser R,Holliday JE,Moeschberger ML,Schaller JP

doi

10.1021/jm00366a004

subject

Has Abstract

pub_date

1983-12-01 00:00:00

pages

1679-86

issue

12

eissn

0022-2623

issn

1520-4804

journal_volume

26

pub_type

杂志文章

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