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Optimization of the Schiff bases of N-hydroxy-N'-aminoguanidine as anticancer and antiviral agents.

Abstract：

:Hydroxyurea, hydroxyguanidine, and some thiosemicarbazones have been shown to have anticancer and antiviral activities. One of their possible sites of action is the enzyme ribonucleotide reductase (RR). Combination of the structural features of these compounds led to the design and synthesis of the Schiff bases of N-hydroxy-N'-aminoguanidine. Synthesis and structure-activity studies of some of these compounds point to increased size and lipophilicity as important factors for activity. To optimize the activities of this series of compounds, 13 derivatives of high lipophilicity and molecular size have been synthesized and their biological activities studied. The most active anticancer compounds against L1210 in vitro (compounds 9 and 12) are about 7 times more active than hydroxyguanidine and hydroxyurea. The most active antiviral compounds against Rous sarcoma virus transformation of chick fibroblasts in vitro (7, 9) are about 40 times more active than hydroxyguanidine. One of the compounds (4) shows promising activity in vivo (% T/C = 140 against P388 leukemia in mice) and is undergoing further studies by the National Cancer Institute (NCI). Studies of the inhibition of transformation of chick embryo cells by Rous sarcoma virus show that all these compounds inhibit transformation while some compounds inhibit viral replication as well.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

T'ang A,Lien EJ,Lai MM

doi

10.1021/jm00146a022

subject

Has Abstract

pub_date

1985-08-01 00:00:00

pages

1103-6

issue

8

eissn

0022-2623

issn

1520-4804

journal_volume

28

pub_type

杂志文章

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