Table 1. Comparative Testing of Fungal Metabolitesa.
| BoNT/A
protease assay |
MPNHDAb |
||||
|---|---|---|---|---|---|
| % inhibition
(μM) |
paralytic
timed (μM) |
||||
| sample | 100 | 20 | IC50c (μM) | 20 | 2 |
| chaetochromin A (1) | 74.0 | 55.0 | 24.6 | 187.8e | 104.0 |
| talaroderxine A (2) | 96.0 | 85.0 | 3.7 | 197.0e | 188.7e |
| talaroderxine B (3) | 80.3 | 67.0 | 10.1 | 94.7f | 174.3e |
| secalonic acid (4) | 64.5 | 39.1 | 28.6 | 67.0 | NDg |
| cephalochromin (5) | 72.0 | 45.0 | 29.2 | 59.0 | NDg |
| skyrin (6) | 74.3 | 40.3 | 31.5 | 81.0 | 64.0 |
| CB 7969312h (control) | 98.0 | 96.2 | 2.1 | 300.0 | 300.0 |
a
Assays conducted as described in ref (1) and the Supporting Information.
b
Mouse phrenic nerve hemidiaphragm assay.
c
IC50 (50% inhibitory concentration) values were determined from nine concentrations of each compound using GraphPad Prism 4 (GraphPad Software, La Jolla, CA).
d
Average time to 50% loss of twitch tension (min); average value for BoNT/A toxin control, 62 min.
e
P value <0.01 (highly significant) in comparison with values recorded for the BoNT/A control; statistical analyses were performed using SigmaPlot 10 (Systat Software, San Jose, CA).
f
Solubility issues in the test medium at this concentration rendered this value unreliable.
g
Not determined.
h
A small molecule inhibitor described in ref (1).