Where Else Have the Aryl Pyrroles been Evaluated?

17 Oct
Published by MatTodd



Last week I was talking with Lei Liu from Tsinghua University, who was visiting Sydney to give a talk on his synthetic methodology research. I showed him the compounds that are the starting point of the open source drug discovery project for malaria, the arylpyrrole set. He said he'd seen these compounds before, in a different context, and after a little searching around we found the relevant paper here. Compounds very similar to the GSK arylpyrrole set have been found to be active against the proteasome.
This biological activity is interesting. Does this imply a possible mechanism of action for the arylpyrrole series, whose mechanism of action is unknown?
The occurrence of these compounds in a study unrelated to the GSK malaria study is not surprising because the arylpyrroles were part of a commercial library, not arising from an internal GSK project. Thus the hits against the proteasome were (presumably) from a commercial library also, which may have been optimized.
If the hits have been optimized, it would be useful to access those analogs from the group that published the proteasome paper, and have them screened for antimalarial activity. We will contact them, unless anyone already knows them.
What this also implies, apart from the value of talking to random people about science, is that there may be other studies out there where molecules related to the arylpyrrole set are being made and evaluated, but not for malaria. We need to identify those projects and somehow access small amounts of the relevant compounds, to speed up our evaluation of the series. Any advice gratefully received - it would be great if anyone wanted to do some searching around for groups working on such compounds.