Structure-based discovery of inhibitors of the YycG histidine kinase: New chemical leads to combat Staphylococcus epidermidis infections

Table 2 Biological effects of seven potential inhibitors of the YycG histidine kinase

Chemical inhibitors	MICs (μM) ^a	K_Dvalue (μM) ^b	IC₅₀ (μM) for YycG' ^c	CC₅₀ (μM) on Vero cell ^d	Hemolysis (%) ^e
Compound 1	50	27.8	48	>200	< 0.1 (< 0.1)
Compound 2	25	11.1	29	96	2.3 (6.1)
Compound 3	12.5	40.4	15	152	< 0.1 (0.5)
Compound 4	12.5	2.8	13.5	>200	0.1 (0.4)
Compound 5	6.25	2.3	14	>200	0.1 (0.3)
Compound 6	100	--	>200	>200	1.1 (2.3)
Compound 7	0.2	15.7	6.5	>200	< 0.1 (< 0.1)

^a The concentrations (μM) listed here were equal to those listed in Table 2, as tested on S. epidermidis ATCC 12228.
^b K_Dvalue represents the binding affinity of various inhibitors to the YycG' protein, compound 6 showed a very low binding affinity, and could not calculate its K_Dvalue with software.
^c IC₅₀ represents the concentration of inhibition of 50% the YycG' protein autophosphorylation. As the highest concentration tested was 50 μM, compound 6 displayed poor ability of inhibition.
^d CC₅₀ represents the concentration that produce a 50% cytotoxicity effect on Vero cell, as the highest concentration tested corresponding to 200 μM.
^e The healthy human erythrocytes were used for the hemolysis assay, and the hemolytic activity of seven inhibitors were shown at their MICs and 4 × MICs (the numbers in the parenthesis) for S. epidermidis ATCC12228 strain.

ISSN: 1471-2180