Depletion of Polyamines Potentiates the Antitumour Effect of Tetracyclic Amidines Bearing a Putrescine Moiety

Abstract

D, L-2-(Difluoromethyl) ornithine (DFMO), a potent inactivator of putrescine biosynthesis that depletes spermidine levels in cells, is known to enhance cytotoxicity of DNA-binding drugs. A significant in-vitro cytotoxicity and DNA-binding affinity found for amidines containing both heterocyclic and polyamine moieties prompted us to evaluate their in-vivo activity on Lewis lung carcinoma (3LL). When administered alone to tumour bearing mice, neither DFMO nor the tetracyclic amidines were effective. However, their combined administration with DFMO inhibited tumour growth significantly.