PMID: 857019May 1, 1977

Study of trans-cyclopropylbis (diketopiperazine) and chelating agents related to ICRF 159. Cytotoxicity, mutagenicity, and effects on scheduled and unscheduled DNA synthesis

Journal of Medicinal Chemistry
D T WitiakR E Gibson

Abstract

The cytotoxicity, mutagenicity, and DNA damaging potential of trans-cyclopropylbis (diketopiperazine) (3) and chelating agents related to ICRF 159 (1) were examined as a function of concentration and duration of exposure in the Chinese hamster cell line V79A. At a concentration of 10(-3) M, 1 and the trans-cyclopropanediamine tetraacid 8 and ester 7 proved to be cytotoxic and mutagenic. The trans-cyclopropyl analogue 3 of ICRF 159 and acyclic tetraacid 6 were less cytotoxic at all concentrations; analogue 3 exhibited no mutagenic activity at any of the concentrations tested. Compounds 1, 7, and 8, at lethal concentrations, exhibited significantly different mutation frequencies with 7 being sixfold more mutagenic than 8 at the same molar concentration. At 10(-3) M compounds 8 was several times more effective blocking DNA replication than other analogues but did not induce unscheduled DNA synthesis as did 1,3, and 6. With the exception of 8, there was an excellent correlation between mutagenesis and the induction of unscheduled DNA synthesis.

Citations

Jan 1, 1990·Cancer Chemotherapy and Pharmacology·T NaritaS Tsukagoshi
Nov 17, 1986·Biochimica Et Biophysica Acta·Y Okuno, J Gliemann
Sep 12, 2013·International Journal of Pharmaceutics·Katarzyna RegulskaMiłosz Regulski
Sep 28, 1998·Biochimica Et Biophysica Acta·T Andoh, R Ishida
Aug 1, 1978·Photochemistry and Photobiology·R W HartF B Daniel
Feb 1, 1982·Photochemistry and Photobiology·R E Gibson, S M D'Ambrosio
Dec 1, 1983·The British Journal of Dermatology·J J HortonR S Wells
Nov 5, 1997·International Journal of Cancer. Journal International Du Cancer·S GarbisaT Giraldi

Related Concepts

Cell Survival
DNA, Double-Stranded
DNA Replication
Fibroblasts
Clastogens
Piperazines
Razoxane, (R)-Isomer
Molecular Stereochemistry
Structure-Activity Relationship

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