Monthly MycetOS meeting - 22nd October 2024

[KlementineJBS]

22nd Oct 2024: chair: UCL, minute taker: ErasmusMC Will be 12 PM UK/10 PM Sydney - timezones

The Outlook invite can be found https://github.com/OpenSourceMycetoma/Monthly-zoom-meetings/issues/2#issuecomment-1905476888

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: UCL Minute taker: Erasmus MC Previous meeting: #26 Recording of today's meeting: Present:

AGENDA AND MINUTES

Screening updates and housekeeping

• [x] most extraneous tabs on the masterlist have been deleted - can Mickey or @wwjvdsande advise on whether the Kinase Library, MMV and EpiChem tabs are to be kept? --> the kinase and MMV tabs should be left. They give data on other compounds which were screened and can be mined if we need to find comparator molecules. E.g. benzimidazoles were also present in the MMV compounds screened
• [ ] @KlementineJBS to share results in relevant sections

Series 1 - Fenarimols

• [ ] @mattodd to capture on wiki pages the desirable compounds identified in the Fenarimol paper, e.g. the meta-substituted derivatives.
• [ ] @mattodd to submit the paper (after checking final list of To Dos here.

Series 2 - Aminothiazoles

• @KlementineJBS can share finalised IC50 results / they have been added to the SAR page and masterlist

• Uni of York and Whitgift compounds not finalised, but have similar MICs - raw data/ongoing work can be found here

• @eloizidou to report back on any literature work on MoA that has been carried out by students. @wwjvdsande has created a page to communicate about this more clearly (see here). See below.

• [ ] @fantasy121 to add his thesis to GitHub + add info on MOA from his thesis to relevant repositories

• @KlementineJBS has found a group that may have samples we should test (https://github.com/OpenSourceMycetoma/Series-2-Aminothiazoles/issues/28) and is asking for advice on which compounds and how to reach out.

• [ ] has @dosreic been able to send the samples described here ?

• [ ] @P-Rayner to give update on the group of students who are making aminothiazoles

  Series 3 - Phenothiazines

• very few hits from high-concentration testing of Uni of York's latest batch (see here - results will be finalized within 1-2 weeks)

• [x] @DouniaEMC to add toxicity data for NEU/Curaxin compounds to Wiki

• [ ] are @P-Rayner and co still planning on making the curaxin-137 scaffold hops as suggested by @MFernflower ?

• [ ] has @lferrins been able to send any more MYOS626, 627 and 628?

Series 5 - Benzimidazoles and benzoxazoles

• any updates from @MA-Jjingyi or @AndreaOtago on the paper? Ma posted an update about the SAR/results in #26
• Andrea needs to know what journal we want to aim this paper at (for formatting/references)
• [ ] Klementine to rename compounds as Series 5a/5b in masterlist
• [ ] has @AndreaOtago been able to make a list/figure of desired compounds? These can be posted as an issue on the Series 5 repository OR on the What-molecules-to-screen repository (and then shared to the "Potential projects" page here --> currently private, needs to be unlocked by @mattodd <-- this has been done, now public.

Series 6 - Ketoximes

• last meeting, Dmitrij presented his SAR findings. Majors conclusions are: big differences between isomers, E isomer is more potent that the Z isomer, Oxiconazole nitrate (Z) isomer shows the best IC50, second best is compound 104-(E). The conclusions and diagrams need to be added to the Series 6 wiki, e.g. here.
• [ ] Dmitrij to share thesis here when finalised

Biology

• updates from @DouniaEMC at Erasmus MC
• Tim to update on collaboration with UNC Chapel Hill

General

• Vijay offered that if the activity data for these ketoxime derivatives are provided, he can do QSAR analysis using Pydescriptor. He can also do AI runs.
• we need to generate different document with ketoximes so Vijay can test them, he just needs IC50 and structures. Can we have volunteers to generate these for each series?
• @bebi78 suggested looking into agricultural fungicides for new compounds - this could perhaps lead to a collaboration and be a possible source of funding. Who can look into this?

AOB

Next meeting

26 November 2024: chair: USyd, minute taker: UCL 8 a.m. London, 9 a.m. Europe, 7 p.m. Sydney Timezones

[KlementineJBS]

We are joining on the UCL zoom link today

[MFernflower]

The four series 3 compounds that we requested more of from Lori:

[eloizidou]

Group project_summary of findings.pptx This the summary of activities of aminothiazole analogues against HDAC, 20S proteasome and PI3K enzymes from the UCL MSc projects this summer.

[bebi78]

@KlementineJBS @P-Rayner Here is the already tested series 2 amine compound I mentioned in the meeting, available by reductive amination (via Schiff base intermediate).

[MFernflower]

@OpenSourceMycetoma/corecontrib Have N-alkylated aminothiazoles been tried? E:G

[MFernflower]

2-(Methylamino)pyridine seems to be commercially available so this might be good target for highschool to make?

@KlementineJBS