mattodd
commented
3 years ago Re my action item: I finally uploaded Rosalyn Chan's very nice thesis that includes all this work - sorry for the delay. The thesis is here with a CC-BY licence. It includes an analysis of the grain structure (thanks for all your help @wwjvdsande ) and assessment of whether there is correlation between potency and physicochemical parameters like logD and size. Concludes with the design of an assay we might want to consider for measuring grain penetration. Rosalyn has now graduated, but a new project student is incoming and I was thinking we could do worse than consider what is known about molecular penetration in other biofilm-like structures? i.e. what we might want to do to modify the fenarimols so that they go where we want them (while maintaining potency). The new student (Jia Lau) just joined Github and I'll ask them to start an issue to outline the project.
wwjvdsande
MOUSEY007
KYM384
MFernflower
This meeting follows on from the previous meeting (#28)
When: Tuesday 29th September 2020 at 4 pm AEST (Sydney, Australia)
Where: Held through Zoom
Who: @fantasy121, @kym834, @wwjvdsande, @MKonings, @Wilson-Lm, @mattodd, Peter Rutledge, @MFernflower, @dmitrij176, @alintheopen
Recording of the meeting Open Source Mycetoma Meeting 3 – 29 September 2020 - YouTube. Copy of chat here.
Setting up MycetOS monthly meetings - Suggested by @mattodd (#31). @fantasy121 and @kym834 will coordinate these meetings and @Wilson-Lm to do promotions before and after the meetings on twitter. Time currently is 2 am in US. Will find a more friendly time slot. Probably won’t be able to accommodate everyone but may set up alternating time slots to share the late nights/early mornings.
Ameoba progress - sent off compounds (2 active and 2 inactive). @MOUSEY007 posted: not great activity so not going to pursue further. Important result to add into our paper. New question - will these drugs be specific for eumycetoma or will they have other uses against other fungal infections? Can screen against a number of other microorganisms and causative agents for eumycetoma and causative agents for other diseases. There are a couple of examples of causative agents that are not inhibited by Itraconazole. All of this is good to show the boundaries of the drug. Question: who to do such testing?
Team Erasmus update - 11 analogues set for /in vivo Galleria mellonella/ model. Slight delay due to issues with /in vivo/ model due to change in supplier. Tested the toxicity of these compounds, excluding 3 samples sent in June, found they are not toxic. There are 10 incoming analogues from Ghana that will be send soon for testing.
Team UCL update - Completed and confirmed 2 new analogues and collected all data for the manuscript. Proposing an 8-oxa-3-azabicylcoc[3.2.1]octane compound and re-synth some aldoximes identified by Wendy in the Pandemic Response Box screen.
Team USYD update - @fantasy121 has synthesised some new analogues without the pyridin-3-yl. New compounds with cyclohexane and phenyl as the third ring structure. Kymberley has started synthesis of some phenylpiperazine based compounds, up to the final step.
Series 2 - Need to find out if we can get some aminothiazoles donated as these are commonly explored before we start committing to synthesis. @MFernflower found a paper that showed them to be active against MTB via targeting glycolysis - thinks most likely MOA is via inhibition of either enolase or succinate dehydrogenase. Should we test a succinate dehydrogenase inhibitor (SDHI) against mycetoma as a sanity check? @wwjvdsande will look into purchasing a SDHI to test.
AOB:
Action Items:
Next meeting
When: Tuesday October 27th, time TBD.