wwjvdsande
commented
4 years ago Hi @kym834 @bendndi @drc007, MMV006357, MMV675968 and MMV022478 all had potent in vitro and in vivo activity. In the larvae model they performed well. For these compounds the in vivo activity has therefore been proven and in my opinion they would be good starting points for new compound series. If you would willing to make a series out of MMV006357 we could certainly screen in in vitro in the wintertime and than start testing in vivo when the spring comes.
bendndi
drc007
MFernflower
kym834
For strain mm55 we had an IC50 of 0.092 ug/ml. The MIC was 4 ug/ml. MICs for 7 other strains ranged were also 4 or 8 ug/ml. The MIC50 was 4 ug/ml. The IC50 measured for M. mycetomatis was comparable to the IC50 of Trichophyton mentagrophytes (IC50 of 0.1 ug/ml) (Nose et al., J Bact, 1971, p 176-184). 
It was part of the pandemic box. If did not inhibit M.mycetomatis growth at 25 uM and was therefore not tested further. Which compound do you prefer to have tested as well?
PaulMcKeatingSevenoaks
Hi @bendndi @drc007 @wwjvdsande,
I've had a look at the synthesis of MMV006357 and would be happy to resynthesis it here at The University of Sydney and ship to @wwjvdsande & co. so that the activity can be confirmed and kick off this series. Is there still an interest in pursuing it?
I was also wondering, in regard to doing some synthesis for a SAR study, would the activity need to be confirmed in vitro and in vivo before we set about synthesising some analogues in which case we would have to wait until the northern hemisphere summer for in vivo testing results? Or, would activity confirmation in vitro be enough that we could start exploring the synthesis of analogues sooner?