Table 3.

Evaluation of azide 2, anti-triazoles 1 (SOL) and 19–32 using minimum inhibitory concentration (MIC) assays (μg/mL) against E. coli and S. pneumoniae strains. Compounds are rank-ordered by potency in MIC assays against E. coli then S. pneumoniae strains. MIC values determined in three independent experiments; translation values in two independent experiments. Analysis of the data in Table 3 reveals that the poorest-performing compounds (32, 20, and 29, shown in red) against both strains correlate with the binding data; in fact, 20 and 29 had the highest K_d values. The polarity of 29 and 32 may be contributing to poor uptake and/or permeability. Predictive indices (PIs) are calculated for the MICs against each strain with respect to K_d values.

Cmpd	Kd (nM)	ΔG (kcal/mol)	MIC E. coli DK pKK 3535	MIC E. coli DK A2058G	MIC S. pneumo ATCC 49619	MIC S. pneumo 655 mefA
27	1.8	−11.9	1	1	0.004	0.5
19	1.1	−12.2	2	1	0.002	0.5
28	1.5	−12.0	2	2	0.032	4
SOL (1)	0.6	−12.6	2	2	0.006	0.375
Azide 2	2.1	−11.8	2	2	0.002	0.25
24	1.4	−12.1	2	2	0.005	1
26	2.5	−11.7	2	2	0.002	0.5
25	1.1	−12.2	2	2	0.016	0.5
22	1.7	−12.0	2	4	0.004	1
23	1.3	−12.1	4	4	0.008	1
21	1.6	−12.0	4	4	0.016	1
31	2.4	−11.7	4	4	0.016	2
30	2.5	−11.7	4	4	0.032	2
20	3.5	−11.5	4	4	0.016	2
32	0.8	−12.4	8	8	0.063	4
29	5	−11.3	32	32	4	4
PI	N/A	N/A	0.46	0.48	0.34	0.44