Open meeting for schools/universities - March 2024

[KlementineJBS]

Hi @OpenSourceMycetoma/corecontrib and others,

we'd like to have a meeting to discuss what compounds are being made by students across the globe, especially now that we have three different series being made!

Please tag anyone that I've missed who might be interested in joining.

I believe we currently have: Series 2 (aminothiazoles) - @AndyBishopSevenoaks @PaulMcKeatingSevenoaks @Whitgift @eloizidou @katieterrett @P-Rayner @JuliaSarju Series 3 (tricyclics/phenothiazines) - @P-Rayner @JuliaSarju Series 5 (benzimidazoles) - @AndreaOtago

Meeting details

Time: 8 pm March 11th UK time, March 12th AUS/NZ time (12 noon UK) Timezones

Location: https://uni-sydney.zoom.us/j/88573014757?from=addon

Chair: USyd Minute taker: need a volunteer please!

Agenda

1. Introductions - name, institution, year group that you work with, types of molecules you're making, timeframes

2. Series 2 summary - Erika?

• interesting results so far
• SAR
• plans for future work

3. Series 3 summary - Peter?

• see above

4. Series 4 summary - Andrea?

• see above

5. Logistics

• coordinating with schools
• using GitHub to share data
• sharing of emails for future meetings

[KlementineJBS]

Choose a time and date

Put your name next to any times that work well for you. Please feel free to add others/suggest a different week to meet, keeping in mind timezones.

Monday March 11th (9 am UK, 8 pm SYD, 10 pm NZ) Monday March 11th (8 pm UK, 7 am SYD, 9 am NZ) I am unsure what timezone the day of Monday is in, if this is 8pm UK on a Monday this means it is Tuesday morning in NZ. So yes for Andrea if this is Tues 12 march 9am NZ time. @P-Rayner

Tuesday March 12th (9 am UK, 8 pm SYD, 10 pm NZ) @P-Rayner Tuesday March 12th (8 pm UK, 7 am SYD, 9 am NZ) @P-Rayner

Wednesday March 13th (9 am UK, 8 pm SYD, 10 pm NZ) Wednesday March 13th (8 pm UK, 7 am SYD, 9 am NZ) Andrea (if 9am Thurs 14 NZ time). @P-Rayner

Thursday March 14th (9 am UK, 8 pm SYD, 10 pm NZ) Andrea @P-Rayner Thursday March 14th (8 pm UK, 7 am SYD, 9 am NZ) Andrea @P-Rayner

[AndreaOtago]

This year some Otago students are again making benzoxazoles (primarily for a DNDi project but also sent in here), just FYI although I think grouped under series 5 'benzimidazoles' they are not benzimidazoles. You could also include @csuth22 Charlotte at Imperial, she may also be making/have made some novel benzoxazoles with material spare.

[eloizidou]

Hi Klementine,

Please see my availability:

Monday March 11th (9 am UK, 8 pm SYD, 10 pm NZ) – Erika Loizidou available Monday March 11th (8 pm UK, 7 am SYD, 9 am NZ) - Erika Loizidou available

Tuesday March 12th (9 am UK, 8 pm SYD, 10 pm NZ) - Erika Loizidou available

Thursday March 14th (9 am UK, 8 pm SYD, 10 pm NZ) – Erika Loizidou available Thursday March 14th (8 pm UK, 7 am SYD, 9 am NZ) – Erika Loizidou available Best wishes Erika

Erika Loizidou, PhD, FRSC, SFHEA Lecturer (Teaching) Drug Discovery Department of Pharmaceutical and Bio Chemistry Room B06 UCL School of Pharmacy 29-39 Brunswick Square London, WC1N 1AX, UK

From: Klementine Burrell-Sander @.> Sent: Wednesday, February 28, 2024 1:38 AM To: OpenSourceMycetoma/Monthly-zoom-meetings @.> Cc: Loizidou, Erika @.>; Mention @.> Subject: Re: [OpenSourceMycetoma/Monthly-zoom-meetings] Open meeting for schools/universities - March 2024 (Issue #18)

⚠ Caution: External sender

Choose a time and date

Put your name next to any times that work well for you. Please feel free to add others/suggest a different week to meet, keeping in mind timezones.

Monday March 11th (9 am UK, 8 pm SYD, 10 pm NZ) Monday March 11th (8 pm UK, 7 am SYD, 9 am NZ)

Tuesday March 12th (9 am UK, 8 pm SYD, 10 pm NZ) Tuesday March 12th (8 pm UK, 7 am SYD, 9 am NZ)

Wednesday March 13th (9 am UK, 8 pm SYD, 10 pm NZ) Wednesday March 13th (8 pm UK, 7 am SYD, 9 am NZ)

Thursday March 14th (9 am UK, 8 pm SYD, 10 pm NZ) Thursday March 14th (8 pm UK, 7 am SYD, 9 am NZ)

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[JuliaSarju]

Hi Klementine,

We have also been looking at related carbazole compounds.

In terms of availability I can do: Monday March 11th (8 pm UK, 7 am SYD, 9 am NZ) I am unsure what timezone the day of Monday is in, if this is 8pm UK on a Monday this means it is Tuesday morning in NZ. So yes for Andrea if this is Tues 12 march 9am NZ time.

Wednesday March 13th (9 am UK, 8 pm SYD, 10 pm NZ)

Thursday March 14th (9 am UK, 8 pm SYD, 10 pm NZ) Andrea

[MFernflower]

@P-Rayner @JuliaSarju welcome back! The carbazoles are indeed part of series 3 - I cannot rename the github repository without it breaking things so that is why it still says phenothiazines!

@lferrins data from your carbazole molecules is now in the master list of opensourcemycetoma!!

[JuliaSarju]

Thanks! Good to be back :)

[SianWhitgift]

Hi Klementine,

My availability for Whitgift:

Tuesday March 12th (9 am UK, 8 pm SYD, 10 pm NZ)

Wednesday March 13th (8 pm UK, 7 am SYD, 9 am NZ)

Thanks

Sian —

[KlementineJBS]

It looks like Monday March 11th (8 pm UK, 7 am SYD, 9 am NZ) is our winner - my apologies for not being clearer with this one, for us antipodeans it will indeed be Tuesday morning. I'll make a calendar invite shortly and pin it to the first post.

[KlementineJBS]

Can @mattodd or someone else who has their emails please add the folks from Whitgift and Sevenoaks?

[PaulMcKeatingSevenoaks]

Hi. Will try to do Monday March 11th for Sevenoaks.

[eloizidou]

@KlementineJBS these are the minutes from the school meeting. It's very likely I missed something, can you please check and update as necessary? Many thanks.

Minutes from schools/University meeting March 11th/12th

Present: Klementine Burrell-Sander Peter Rayner Anthony Andrea Vernall Paul McKeating Mat Todd Erika Loizidou

Aminothiazoles (Series 2)

• Klementine plans to make new analogues and at the moment is looking for analogues that can be made from relatively safe starting material so that they can be carried out at a school • Erika updated on the aminothiazole analogues prepared by the MSc students at the UCL School of Pharmacy, in the summer of 2023: o 22 analogues were sent for biological evaluation and of the ones that were tested none showed significant activity. o The next step would be to try to identify targets for these molecules and test for activity either through assays or computationally (when assay kits not available). Possible targets that had been linked to the mechanism of action of series 2 agents are: fungal histone deacetylase enzymes, CYP51, fungal kinases and the fungal proteasome. o Action: Erika needs to look into the assays and tell Klementine whether or how many of the aminothiazole analogues that were synthesized can be tested against any of these targets. o Mat, highlighted the potential of the dihalogenated analogues and asked whether there were any data on the analogues drawn in black (pending evaluation). Action: Klementine to look into this. o Mat, mentioned that Whitgift school will be visiting UCL on March 13th to check the purity of the analogues they synthesized (via NMR and LCMS).

Phenothiazines (Series 3)

• Peter updated us all on his student's work on Series 3
• They have around 30 new molecules and are also looking into substituted phenoxazines and sulfonamide derivatives of phenothiazine.
• The synthesis is simple and suitable for high school students. They can be done in one or two lab sessions and have an easy workup.
• [x] Action: @P-Rayner to upload his 4 protocols for making tricyclics as a sort of "recipe book" on the series 3 wiki page
• [ ] Action: Peter to make some SAR diagrams/tables for phenothiazines once data is available from bio team
• [ ] Action: Erika to discuss with Desiree about the possibility of Whitgift school taking on a phenothiazine analogue. (action completed: Desiree is interested in taking on a molecule and will bring them to contact with Peter and Anthony).

Benzoxazoles (Series 5)

• Andrea updated on the benzoxazole series o Explained how to identify molecules to synthesize from DNDi wanted list of analogues (Open Synthesis Network) o At the moment, they are looking into the pharmacokinetic properties of the analogues they already have before deciding on how to proceed.

• Charlotte at Imperial College is also making benzoxazoles with her students for DNDI -

o Generally, the synthesis of benzoxazoles is easy involved an amide coupling (if coupling agents are used, column chromatography may be needed)

General discussion

• The synthesis of benzoxazole and aminothiazole analogues can be further extended by adding an additional step, i.e a Suzuki coupling. This may be useful for students who are working on this project over several weeks and are assessed on different components.

[KlementineJBS]

Looks great to me @eloizidou, I just added some formatting so that we can see the action points more clearly.

[bebi78]

@KlementineJBS @PaulMcKeatingSevenoaks @mattodd @MFernflower Just wanted to add that the series 2 compound PyrTZ-4SCF3 (MYOS_00508_00_01, DNDI0004039860) showed moderate activity against M. m. (IC50 = 12.9 µM, IC90 = 15.3 µM). Because only one compound of this ´´reductive amination´´ series was prepared and tested so far, it seems to be possible that other substituents than SCF3 might lead to increased activities.

[MFernflower]

I assume one would just change out the para substituted benzaldehyde? @bebi78

[P-Rayner]

Hi all, I've just uploaded the general procedures for the phenothiazine syntheses here. https://github.com/OpenSourceMycetoma/Series-3-Phenothiazines/issues/8

Any questions, the please let me know.