Difluoromethylomithine (DFMO)-peptide conjugates were syntesized as prodrugs to improve the cytotoxic efficacy of DFMO. All conjugates inhibited cell growth n different cell lines more effectively than DFMO itself. The best cytotoxic effect was achieved in all cell lines by DFMO-Glu-His-Phe- Arg-Trp-Gly-OMe, where the carrier peptide is a melanotropin hormone fragment. Although this conjugate is capable of displacing labeled melanotropin from its receptor, its cytotoxic effect on the receptor-positive human melanoma cell line has not been proven to be receptor-mediated. The differences in the cytotoxicities of the congeners seem to be influenced, at least in part, by the nature of the carrier molecule.
ASJC Scopus subject areas
- Pharmaceutical Science