TABLE 1.

Inhibition of PA-Nter by different DKA or DKA-bioisosteric compounds as determined in the plasmid-based enzymatic assay

One microgram of PA-Nter was incubated with 1 μg of M13mp18 plasmid substrate and the compounds. After 2 hours incubation, cleavage was assessed by gel electrophoresis.

Scaffold	Compound	R 1	R 2	IC50a
				μM
Piperidine scaffold	1 (L-742,001)	H	Ph	0.5
	2	Me	Ph	0.5
	3	H	p-F-Ph	1.4
	4	Me	p-F-Ph	0.4
	5	H	Cy	0.5
	6	Me	Cy	0.6
Dihydroxybutenedioic acid	7	—	—	>500
1,3-Dioxo-1-phenylpropane scaffold and triazole bioisostere	8		H	77
	9	Ph	o-OH	>500
Pyrrole scaffold	10 (L-731,988)	H	—	0.8
	11	Me	—	5.5
2,4-Dioxo-4-phenylbutanoic acid (DPBA) scaffold	12	H	H	2.7
	13	Me	H	14
	14	H	o-OMe	2.2
	15	Me	o-OMe	11
	16	H	p-OMe	2.0
	17	H	p-Cl	9.8
	18	H	o-Cl	9.8
	19	Me	o-Cl	15
	20 (L-708,906)	—	—	137
2,4,6-Trioxo-6-phenylhexanoic acid scaffold	21	H	H	>500
	22	Me	H	>500
	23	H	o-OMe	>500
	24	H	o-Cl	>500
Quinolone scaffold	25	H	H	>500
	26	H	CH2CH2OH	>500
	27	H	Bn	>500
	28	Et	Bn	>500
Hydroxypyrimidine- carboxamide scaffold	29	—	—	>500

^aIC₅₀, 50% inhibitory concentration. For each compound the IC₅₀ value was calculated using nonlinear regression analysis. Values are the mean of at least three independent experiments.