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A Synthetic Azinomycin Analogue with Demonstrated DNA Cross‐Linking Activity: Insights into the Mechanism of Action of this Class of Antitumor Agent
Author(s) -
Hartley John A.,
Hazrati Ali,
Kelland Lloyd R.,
Khanim Ruzwana,
Shipman Michael,
Suzenet Franck,
Walker Louise F.
Publication year - 2000
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/1521-3773(20001002)39:19<3467::aid-anie3467>3.0.co;2-t
Subject(s) - mechanism of action , mechanism (biology) , class (philosophy) , dna , chemistry , action (physics) , dna synthesis , computational biology , combinatorial chemistry , biochemistry , biology , computer science , in vitro , philosophy , epistemology , artificial intelligence , physics , quantum mechanics
An efficient synthesis of simplified azinomycin A and B analogues 1 and 2 (see picture) is described, and it is demonstrated that only 1 , bearing both the epoxide and aziridine, induces interstrand cross‐links in double‐stranded DNA. Remarkably, a compound structurally related to 1 but devoid of the aziridine ring exhibited comparable in vitro cytotoxicity, suggesting that in cells the epoxide is largely responsible for the antitumor activity of these agents.