African Journal of
Pharmacy and Pharmacology

  • Abbreviation: Afr. J. Pharm. Pharmacol.
  • Language: English
  • ISSN: 1996-0816
  • DOI: 10.5897/AJPP
  • Start Year: 2007
  • Published Articles: 2273

Full Length Research Paper

Design, Synthesis and biological evaluation of novel acridine-polyamine conjugates against prostate cancer

Hildebert B. Maurice1*, Rodger Phillips2 and Nazira Karodia3
1School of Pharmacy, St. John’s University of Tanzania, P. O. Box 47 Dodoma Tanzania. 2Yorkshire Cancer Research, University of Bradford, West Yorkshire, BD7 1DP, UK 3School of Chemistry and Forensic Sciences, University of Bradford, West Yorkshire, BD7 1DP, UK
Email: [email protected]

  •  Accepted: 04 May 2009
  •  Published: 31 December 2009

Abstract

Prostate cancer is the most common cause of cancer death in men, aged 85 and over. Androgen receptor, a single polypeptide with three functional domains is very important during initiation and progression of the disease. In this study, a DNA intercalating agent, acridine is linked to the testosterone via a polyamine linker to obtain a compound with trifunctional characteristics, where the acridine intercalates the DNA, the polyamine linker binds the phosphoryl groups of the DNA backbone and the testosterone moiety binds into the AR ligand binding domain, with which its DNA binding domain is bound already to the DNA. This trifunctional compound and related derivatives have been synthesized and tested against androgen dependent- and androgen independent- prostate cancer cell lines and they have demonstrated to be cytotoxic at the micromolar concentrations.

 

Key words: Polyamines, Testosterone, Prostate cancer, Acridine, Synthesis.