TABLE 3.

Effects of ODC and AdoMetDC inhibitors on enzyme activities and the survival rate of cultured P. falciparum

Inhibitor	Ki valuea	IC50 (μM) inb:
		P. falciparum culture	Mammalian cell culture
ODC inhibitors
APA	2.7 ± 0.5 (n = 5)	1.0 ± 0.3 (n = 6)	12.8 ± 3.6/24.4c (n = 5)c
CGP 54169A	7.9 ± 2.1d/5.9 ± 1.2 (n = 3/4)	2.0 ± 0.3 (n = 4)	40.8 ± 16.3 (n = 5)
CGP 52622A	20.4 ± 8.1d (n = 3)	2.7 ± 0.2 (n = 5)	12.2 ± 3.2 (n = 5)
DFMO	87,600 ± 14,300d (n = 3)	1,250 ± 420 (n = 4)	NDe
AdoMetDC inhibitors
CGP 40215A	0.8 ± 0.2f/1.3 (n = 3/2)	1.8 ± 0.4 (n = 5)	74.4 ± 3.8/>100g (n = 5)
CGP 48664A	3.0 ± 0.9f (n = 3)	8.8 ± 1.7 (n = 5)	0.18 ± 0.07/0.6h (n = 5)
MDL 73811	1.6 ± 0.4 (n = 3)	3.0 ± 0.4 (n = 4)	ND

^aK_i values were determined with recombinant bifunctional P. falciparum ODC-AdoMetDC and/or (as indicated) with the respective separately expressed domains. The data are in nanomolar for the ODC inhibitors and micromolar for the AdoMetDC inhibitors.

^bIC₅₀s were determined in cultured P. falciparum and murine B-cell lymphoma A20/J2 cells 48 h after the addition of the respective inhibitor.

^cData for human T24 bladder carcinoma cells are adopted from reference 34.

^dSeparately expressed ODC domain (21).

^eND, not determined.

^fSeparately expressed AdoMetDC domain.

^gData for human T24 bladder carcinoma cells are adopted from reference 35.

^hData for human T24 bladder carcinoma cells are adopted from reference 30.