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OpenSourceMycetoma / Monthly-zoom-meetings

Since MycetOS is diversifying we decided as from 2023 to place the monthly meetings no longer under a compound series but separately in this repository.
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Mycetoma monthly meeting 28 February 2023 #3

Open wwjvdsande opened 1 year ago

wwjvdsande commented 1 year ago

Time: February 28th (12 noon UK, 1pm EU, 11pm Aus) Timezones.

The Outlook invite can be found here

Location: https://uni-sydney.zoom.us/j/99281549497. In case of failure, use https://ucl.zoom.us/j/99789829423 and in case of double failure use MycetOS meeting teams link Chair: USyd Minute taker: UCL Previous meeting: #1 and recording at ... Recording of this meeting: here

Present: @mattodd @wwjvdsande @bebi78 @fantasy121 @dmitrij176 @MA-Jjingyi and we were joined for the first time by @wosmanitx from George Mason Uni, Virginia (welcome!).

MINUTES

  1. Outstanding items from previous meeting on the fenarimols a) Paper writing
    • [ ] @dmitrij176 @fantasy121 SAR gap analysis and the Epichem library. A refinement of this diagram is needed so that we know whether to request compounds from Epichem for the current paper, or not. i.e. which matched pairs would be instructive in answering questions we have for the current SAR. We need to be clear on which current actives are the comparators. Action still needed on this - can @fantasy121 share the diagram shown in-meeting, clarifying that the known compounds are active. Then we can select ca. 10 compounds to request from Epichem.
    • [ ] @fantasy121 @dmitrij176 Is the chemical experimental section complete (in main paper and in SI document)? Looking at the current draft it looks like there are still remaining issues on the experimental section on the chemistry. If @fantasy121, @dmitrij176 @kym834 could take a look at it and go through it to check the issues highlighted and remove comments when solved. The ppt looks fine. Action: @fantasy121 @dmitrij176 (and ideally @kym834) meet to finalise, and generate copies of these files that are ready to submit to a journal.
    • [ ] Supplemental files for the manuscript: A combined Labarchive offline notebook (not PDF) was suggested as a supplemental file. Action on @fantasy121 @dmitrij176. For the biological supplemental data, which is not in Labarchives, an Excel sheet can be generated from our current Master Lis displaying all data on the fenarimols tested. Action on @MA-Jjingyi and @wwjvdsande.
    • [ ] @mattodd @fantasy121 @dmitrij176 @MA-Jjingyi @wwjvdsande need to double check that all fenarimols made are tested in vitro/vivo and all noteworthy/relevant compounds are included in the manuscript - to ensure we don't accidentally miss key data. If @fantasy121 @dmitrij176 can check if all their molecules are entered in the spreadsheet and sent then @MA-Jjingyi and @wwjvdsande will check if they are screened and are in the manuscript if they are important.
    • [ ] @mattodd to review current paper draft once the above are done.

b) Statistics for in vivo data --> @wwjvdsande will have to contact the statistical department of ErasmusMC. Still needed?

  1. Actions on other compound series: Series 2: aminothiazoles:
    • [ ] Rohan's contribution of compounds from Griffith University QLD: Numbers of compounds, screening capacity, costs and motifs of interest, to be discussed.
    • [ ] Crowdsourcing update - incoming contributions from e.g. @Whitgift, @JuliaSarju, @PaulMcKeatingSevenoaks, Hampton School. Others @kym834 (e.g. Barker College (@katieterrett))? Update on meeting held is here. Actions include a check on compound novelty, and the provision of targets for @Whitgift and @PaulMcKeatingSevenoaks.
    • [ ] Meeting is needed to make sure every school has a different target @mattodd @kym834 Did this happen?

Series 5: Actions based on potencies observed for most recent compound batches_ - e.g. [oxazoles](https://github.com/OpenSourceMycetoma/Series-1-Fenarimols/issues/82#issuecomment-1325150305) oxazoles were selected because they resembled the benzimidazoles which showed potent in vivo efficacy. The oxazoles were validated _in vitro against Madurella mycetomatis and appeared to be very potent. They will be tested against Falciformispora senegalensis too. This series will be evaluated in vivo in the new larval season.

Series 6: ketoximes --> 19 compounds designed. Most of them are synthesized by UCL.

Series natural products.

  1. Other Updates: USYD UCL Erasmus Other sites

  2. Any other business? Was there a discussion needed around the DNDi project described in this paper? Another possible source of molecules here? And also here?

wwjvdsande commented 1 year ago

Can USyd or UCL make the agenda for next week?

dmitrij176 commented 1 year ago

Apologies, but will probably be running late for the meeting.

bebi78 commented 1 year ago

@fantasy121 @mattodd Here is the link to the benzoxazole paper of Andrea and Ben. https://pubs.acs.org/doi/10.1021/acs.jchemed.1c01213

fantasy121 commented 1 year ago

Mind Map of Suggestion for Gap Compounds Mycetoma

fantasy121 commented 1 year ago

@mattodd Here's the chart again. Fixing a few arrow of flow to clarify stuff, I made one or two mistakes. From current SAR, The 4-CF3 position, I'd classified as inconclusive. The 2-F position is what gives good activity imo.

I've rerouted the mind map to address the 4-CF3 gap as well.

KEYS: Oval = we have SAR already (Initial leads were all the starters we had which this series is expanded upon ie the OG leads) dotted box = what we suggested to ask for samples blue boxes A, B, C and D = contested compounds (whether we should ask for samples or not) Arrows = flow of compound comparison like match-pairing etc (ie NOT reaction paths)

So the blue boxes were up for discussions last meeting. Blue A I feel the 4-Cl version (4937) has been represented by the 4-F version (4841), so unless we have the generous number of sample request to work with, either one of these we should request but not both.

Blue B we agreed is no, because it closely matches an inactive SAR, and we don't yet know the alkyl chain addition is good or not.

Blue C I believe we green lighted? these are a bit lower on priority compared to the 2-F,3-F di-sub version (2845, directly above) but actually interesting to explore more di-sub patterns.

Blue D we agreed should be explored.

fantasy121 commented 1 year ago

Did I get that mostly right @OpenSourceMycetoma/corecontrib ?

dmitrij176 commented 1 year ago

@fantasy121 any suggestions on the research paper correction meeting date? Are you available tomorrow?

wwjvdsande commented 1 year ago

@OpenSourceMycetoma/corecontrib I will be speaking at the skinNTD meeting of the WHO in the last week of march. Therefore I will miss the meeting on the 28st of March. Could we either do it one week earlier (21st of March) or can some-one else chair the meeting?

bebi78 commented 1 year ago

@wwjvdsande March 21 would be OK for me.

dmitrij176 commented 1 year ago

@wwjvdsande I agree to 21st of March as well.

bebi78 commented 1 year ago

@mattodd @wwjvdsande Any decision on the next meeting one week earlier?

wwjvdsande commented 1 year ago

@mattodd @fantasy121 if you are able to make it on the 21st too than we do the meeting the 21st. If you can't, you can leave it on the original date.

mattodd commented 1 year ago

21st 12 noon UK time? I think I can do, yes. Mat

On Thu, 16 Mar 2023, 09:06 Wendy van de Sande, @.***> wrote:

@mattodd https://github.com/mattodd @fantasy121 https://github.com/fantasy121 if you are able to make it on the 21st too than we do the meeting the 21st. If you can't, you can leave it on the original date.

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wwjvdsande commented 1 year ago

@OpenSourceMycetoma/corecontrib. Ok I will make a new item. See you all next week! Wendy