Arzneimittelforschung 2002; 52(6): 475-481
DOI: 10.1055/s-0031-1299917
Antibiotics · Antiviral Drugs · Chemotherapeutics · Cytostatics
Editio Cantor Verlag Aulendorf (Germany)

Synthesis and Antitumour Activity of a Series of Cyclic Amidines of 2,3-Dihydro-1H-1,5-benzodiazepines

Regina Jančienė
a   Sector of Application of Biologically Active Compounds, Institute of Biochemistry, Vilnius, Lithuania
,
Lidija Kosychova
a   Sector of Application of Biologically Active Compounds, Institute of Biochemistry, Vilnius, Lithuania
,
Virginija Bukelskienė
b   Sector of Preparative Biochemistry, Institute of Biochemistry, Vilnius, Lithuania
,
Vigintas Domkus
b   Sector of Preparative Biochemistry, Institute of Biochemistry, Vilnius, Lithuania
,
Zita Stumbrevičiūtė
a   Sector of Application of Biologically Active Compounds, Institute of Biochemistry, Vilnius, Lithuania
,
Vida Ragalevičienè
a   Sector of Application of Biologically Active Compounds, Institute of Biochemistry, Vilnius, Lithuania
,
Benedikta D. Puodžiūnaitè
a   Sector of Application of Biologically Active Compounds, Institute of Biochemistry, Vilnius, Lithuania
› Author Affiliations
Further Information

Publication History

Publication Date:
26 December 2011 (online)

Summary

2,3-Dihydro-1H-1,5-benzodiazepine amidines were prepared by nucleophilic substitution of 2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-2-thiones. Evaluation of the 13 synthesised amidines as antitumour agents was carried out in vitro against 60 human tumour cell lines at the National Cancer Institute, Bethesda, USA. The screening revealed a moderate cell growth inhibition of two derivatives on all cell lines at concentrations ranging from l0−5 to 10−4 mol/l. Log P values were theoretically calculated. The more active derivatives were found to exhibit a higher lipophilicity.

Zusammenfassung

Synthese und Prüfung der Anti-Tümor-Wirkung einer Reihe zyklischer Amidine von 2,3-Dihydro-1H-1,5-benzodiazepinen

Einige Amidine von 2,3-Dihydro-1H-1,5-benzodiazepinen wurden durch nukleophile Substitution von 2,3,4,5-Tetrahydro-1H-1,5-benzodiazepin-2-thionen synthetisiert. 13 so hergestellte Amidine wurden am National Cancer Institute (Bethesda, USA) in vitro auf ihre Anti-Tumor-Wirkung gegen 60 Zell-Linien menschlicher Tumore getestet. Zwei Verbindungen zeigten bei Konzentrationen von 10−5 bis 10−4 mol/l eine moderate Hemmung des Wachstums bei allen Zell-Linien. Log-P-Werte wurden theoretisch berechnet. Die Ergebnisse der biologischen Testung lassen den Schluß zu, daß lipophilere Verbindungen höhere Anti-Tumor-Wirkungen aufweisen.