Table 2.
Antimicrobial and Binding Properties
| MIC (μg/mL) | Association constant for 3 | |||
|---|---|---|---|---|
| Compound | S. aureusa | E. faecalisb (VanB) | Ka, M−1 (× 105)c | Δ Δ G b d |
| Vancomycin (1) | 1.25 | 120 | 1.8 (2.3–3.9)e | |
| Vancomycin Aglycon (2) | 1.25 | 40 | 1.4 | - |
| 16 (-Br) | 2.5 | 40 | 1.1 | 0.14 |
| 29 (-OH) | 5 | 40 | 0.53 | 0.57 |
| 30 (-H) | 5 | 80 | 0.68 | 0.42 |
| Permethyl Aglycon Derivatives | ||||
| 7 (-Cl) | 1.25 | 2.5 | 1.3 (2.0) | - |
| 11b (-B(OH)2) | 5 | 10 | 0.23 | 1.03 |
| 14b (-Br) | 2.5 | 5 | 1.1 | 0.1 |
| 18b (-NMe2) | 5 | 10 | 0.34 | 0.79 |
| 19b (-N3) | 1.25 | 5 | 1.2 | 0.05 |
| 20b (-NO2) | >40 | >40 | 0.097 | 1.56 |
| 21b (-CO2CH3) | 2.5 | 10 | 1.0 | 0.16 |
| 22b (-I) | 2.5 | 10 | 1.3 | 0 |
| 23b (-OMe) | 2.5 | 5 | 1.2 | 0.05 |
| 24b (-CN) | 2.5 | 5 | 1.1 | 0.1 |
| 25b (-H) | 5 | 5 | 0.71 | 0.36 |
| 26b (-OH) | 5 | 5 | 0.88 | 0.23 |
| 27b (-CH3) | 2.5 | 5 | 1.2 | 0.05 |
| 28b (-CF3) | 2.5 | 20 | 1.2 | 0.05 |
a
Vancomycin-sensitive Staphylococcus aureus (ATCC 25923).
b
Vancomycin-resistant Enterococcus faecalis (VanB, ATCC 51299).
c
Binding to N,N′ -Ac2-L-Lys-D-Ala-D-Ala (3).
d
The free energy of binding (ΔΔGb) was tabulated from the experimentally determined Ka using the equation ΔΔGb = RTlnK, where K=1Ka/xKa; 1Ka is the association constant for the complex of 2 or 8 with 3; xKa is the association constant for the complex of compound X with 3.
e
Taken from ref 8a.