| In vitro study | Eflornithine (D/L-DFMO) is an inhibitor of ODC, the first enzyme in eukaryotic polyamine biosynthesis. Both enantiomers of Eflornithine (DFMO) irreversibly inactivate ODC. Both Eflornithine enantiomers (L-Eflornithine and D-Eflornithine) suppress ODC activity in a time- and concentration-dependent manner. The inhibitor dissociation constant (K D ) values for the formation of enzyme-inhibitor complexes are 28.3±3.4, 1.3±0.3 and 2.2±0.4 µM respectively for D-Eflornithine, L-Eflornithine and Eflornithine. The inhibitor inactivation constants (K inact ) for the irreversible step were 0.25±0.03, 0.15±0.03 and 0.15±0.03 min -1 respectively for D-Eflornithine, L-Eflornithine and Eflornithine. Treatment of human colon tumour-derived HCT116 cells with either L-Eflornithine or D- Eflornithine decreases the cellular polyamine contents in a concentration-dependent manner. The enantiomers display different potencies in vitro, with the L-enantiomer having up to a 20-fold higher affinity for the target enzyme ornithine decarboxylase. The L-Eflornithine also appears to be more potent in cultured T.brucei gambiense parasites. |
