Aromatic bis-N-hydroxyguanidinium derivatives: synthesis, biophysical, and biochemical evaluations.

Abstract

In this paper we report the synthesis of a new family of hydroxyguanidinium aromatic derivatives (4a-g) as potential minor groove binders and cytotoxic agents. Their DNA affinity was evaluated by thermal denaturation experiments using salmon sperm DNA. The antiproliferative effects of derivatives 4a, 4d, and 4f were evaluated in human promyelocytic HL-60, breast carcinoma MCF-7, and neuroblastoma Kelly cell lines using the AlamarBlue viability assay, and IC(50) values were obtained. All three compounds were active in the HL-60 cell line. In particular, 4b exhibits antiproliferative effects in all three cell lines while 4d reduced HL-60 and Kelly viability. Both 4b and 4d produced considerable antiproliferative activity in the Kelly cell line. Derivative 4d was chosen for further cell cycle and apoptosis studies using flow cytometric analysis of cellular DNA content.

• Authors: Amila Kahvedžić, Seema-Maria Nathwani, Daniela M Zisterer, Isabel Rozas
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 56 Issue 2 Pg. 451-9 (Jan 24 2013) ISSN: 1520-4804 [Electronic] United States
• PMID: 23252648 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Guanidines
• Hydroxylamines
• hydroxyguanidine

Topics

• Biophysics
• Cell Line
• Guanidines (chemical synthesis, chemistry, metabolism)
• Humans
• Hydroxylamines
• Magnetic Resonance Spectroscopy
• Mass Spectrometry