Table 1.
Physicochemical properties and biological data of andrographolide and derivatives.
|
Compd |
logD7.4 [a] |
TPSA[b] [Å2] |
%PPB[c] |
MM‐GBSA ΔG Bind[d] [kcal/mol] |
ARE specificity ratio, SR[e] |
Vero‐E6 plaque reduction assay NT50 [f] [μM] |
|---|---|---|---|---|---|---|
|
1 |
1.4 |
87 |
88 |
−26.2 |
19.4 |
1.4 |
|
2 |
2.4 |
67 |
93 |
−29.4 |
5.7 |
>10 |
|
3 |
2.4 |
67 |
93 |
−31.8 |
n.d.[g] |
>10 |
|
4 |
n.d. |
n.d. |
n.d. |
−45.8 |
n.d. |
n.d. |
|
9 |
1.4 |
87 |
88 |
−29.4 |
211 |
2.1 |
|
11 |
n.d. |
87 |
n.d. |
n.a.[h] |
n.d. |
>10 |
|
16 a |
1.9 |
96 |
83 |
−27.3 |
35.6 |
3.7 |
|
16 b |
2.5 |
96 |
38 |
−36.4 |
10.8 |
8.1 |
|
16 c |
1.3 |
133 |
92 |
n.a. |
13.3 |
>10 |
[a] Experimental distribution coefficient at pH 7.4. [b] Topological polar surface area. [c] Plasma protein binding values were estimated by an HPLC‐based method. [d] An estimate for the binding affinity derived from computational docking. The estimate does not include contributions from the covalent interaction. A more negative value indicates stronger binding. [e] SR≤1, not specific; 1≤SR≤10, moderately specific; 10≤SR≤100, specific; 100≤SR, highly specific. See also equation 4 in the Supporting Information. [f] Analyte titers at which 50 % neutralization (NT50) was recorded. [g] Not determined. [h] Not available. The binding affinity cannot be reliably estimated: 11 is a non‐electrophilic compound; 16 c has a long and flexible solvent‐exposed linker.