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Series 2
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Aminothiazole analogues synthesized by Whitgift school 2024 #27

Open eloizidou opened 5 months ago

eloizidou commented 5 months ago

MYOS432 analysed by NMR and LCMS on March 2024 when students and teachers visited UCL School of Pharmacy. MYOS432 J+H.pdf JW+SC.pdf KSY+RC.pdf Q+Y.pdf Sam.pdf Summary of NMR plots.docx

MYOS605 analysed by NMR and LCMS on June 2024 during the second visit of students from Whitgift school at UCL School of Pharmacy. In vivo activity: percentage growth of M.mycetomatis at 100μΜ: 180.2 ± 42.2 and 25μΜ: 153.1 ± 100.7 MYOS605

AB+ZI.pdf AS+PO.pdf JW+BV.pdf KSY+RC.pdf Mark + Harry.pdf Q+Y.pdf whitgift240619_AB_ZI1.pdf whitgift240619_AB_ZI2.pdf whitgift240619_AS_PO_1.pdf whitgift240619_AS_PO_2.pdf whitgift240619_harry1.pdf whitgift240619_harry2.pdf whitgift240619_JW_BV_1.pdf whitgift240619_JW_BV_2.pdf whitgift240619_KSY_RC_1.pdf whitgift240619_KSY_RC_2.pdf whitgift240619_Q_XI_1.pdf whitgift240619_Q_XI_2.pdf

eloizidou commented 5 months ago

The next molecule to be synthesized by Whitgift is:

Whitgift molecule 3

KlementineJBS commented 4 months ago

Interesting that MYOS605 had such poor in vitro activity despite having the pyridine rings on both sides! I've updated the Wiki with these results and Whitgift's new target.

eloizidou commented 4 months ago

@Klementine @.***> yes I agree. It may be good to send the MYOS605 Whitgift sample to tested, the reported activity was from the same molecule synthesized in the past.

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: Thursday, June 27, 2024 5:32 AM To: OpenSourceMycetoma/Series-2-Aminothiazoles @.> Cc: Loizidou, Erika @.>; Assign @.> Subject: Re: [OpenSourceMycetoma/Series-2-Aminothiazoles] Aminothiazole analogues synthesized by Whitgift school 2024 (Issue #27)

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Interesting that MYOS605 had such poor in vitro activity despite having the pyridine rings on both sides! I've updated the Wiki with these results and Whitgift's new target.

— Reply to this email directly, view it on GitHubhttps://github.com/OpenSourceMycetoma/Series-2-Aminothiazoles/issues/27#issuecomment-2193673565, or unsubscribehttps://github.com/notifications/unsubscribe-auth/BC3PBSC2A6ZXRBDEKQFJCQ3ZJOIVFAVCNFSM6AAAAABJVO7JXKVHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMZDCOJTGY3TGNJWGU. You are receiving this because you were assigned.Message ID: @.***>

KlementineJBS commented 2 months ago

Hi @eloizidou - do you know when Whitgift will be ready to send the fluoro analogue they're working on? And also, whether you would be able to send the MYOS605 molecule that Whitgift made along with the new one?

eloizidou commented 2 months ago

Hi Klementine, I can send MYS605 and the other Whitgift molecule this week. Can you please send me the address details? Regarding the fluoro analogue, Whitgift will start the synthesis in February 2025, so I think we can send it by March/April.

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: Tuesday, September 10, 2024 2:28 PM To: OpenSourceMycetoma/Series-2-Aminothiazoles @.> Cc: Loizidou, Erika @.>; Mention @.> Subject: Re: [OpenSourceMycetoma/Series-2-Aminothiazoles] Aminothiazole analogues synthesized by Whitgift school 2024 (Issue #27)

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Hi @eloizidouhttps://github.com/eloizidou - do you know when Whitgift will be ready to send the fluoro analogue they're working on? And also, whether you would be able to send the MYOS605 molecule that Whitgift made along with the new one?

— Reply to this email directly, view it on GitHubhttps://github.com/OpenSourceMycetoma/Series-2-Aminothiazoles/issues/27#issuecomment-2340785964, or unsubscribehttps://github.com/notifications/unsubscribe-auth/BC3PBSFR5UQS6ZY3B4PXLHDZV3XW5AVCNFSM6AAAAABJVO7JXKVHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMZDGNBQG44DKOJWGQ. You are receiving this because you were mentioned.Message ID: @.***>

KlementineJBS commented 2 months ago

ErasmusMC Medical Microbiology and Infectious Diseases T.a.v. Ger Roedelof, Klementine Burrell-Sander en Wendy van de Sande Gebouw NB Kamer NB 920 Westzeedijk 353 3015 AA Rotterdam The Netherlands Contact: Wendy van de Sande Phone: +31 10 703 35 10 Email: [w.vandesande@erasmusmc.nl]

KlementineJBS commented 1 month ago

Hi @eloizidou - we have received the compounds and I'll start screening them this week. Can you tell me where the results for MYOS605 have come from if you're only sending the compound to us now? I'm confused!

(Also, I assume you mean in vitro activity, not in vivo!)

eloizidou commented 1 month ago

Hi @Klementine @.***> thanks for confirming receiving the compounds. Please ignore the activity values for MYOS605. I got them from the masterlist but I double checked and it looks like they refer to another compound (A3B1) that was originally given that code and later the code was removed due to duplication.

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: Tuesday, September 24, 2024 9:38 AM To: OpenSourceMycetoma/Series-2-Aminothiazoles @.> Cc: Loizidou, Erika @.>; Mention @.> Subject: Re: [OpenSourceMycetoma/Series-2-Aminothiazoles] Aminothiazole analogues synthesized by Whitgift school 2024 (Issue #27)

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Hi @eloizidouhttps://github.com/eloizidou - we have received the compounds and I'll start screening them this week. Can you tell me where the results for MYOS605 have come from if you're only sending the compound to us now? I'm confused!

(Also, I assume you mean in vitro activity, not in vivo!)

— Reply to this email directly, view it on GitHubhttps://github.com/OpenSourceMycetoma/Series-2-Aminothiazoles/issues/27#issuecomment-2370632247, or unsubscribehttps://github.com/notifications/unsubscribe-auth/BC3PBSALIOROOYY6DUEDFZLZYEQHPAVCNFSM6AAAAABJVO7JXKVHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMZDGNZQGYZTEMRUG4. You are receiving this because you were mentioned.Message ID: @.***>

KlementineJBS commented 1 month ago

No worries @eloizidou ! I've removed that data from the masterlist now, and the good news is that it looks like MYOS605 has better activity than those mistaken results :)

MFernflower commented 1 month ago

@eloizidou @OpenSourceMycetoma/corecontrib

I wonder if it would be worth trying to make something like this since it is quite different from our normal SAR https://github.com/OpenSourceMycetoma/Series-2-Aminothiazoles/blob/master/amide_click_chem.png

KlementineJBS commented 1 month ago

@MFernflower those are some of the compounds that Pieroni's group has made, as I mentioned here

but if we can't get them from Pieroni, I think @P-Rayner might be able to make some with his cohort?

P-Rayner commented 1 month ago

@MFernflower @KlementineJBS. I really like these compounds. We have some plans to make a small series of compounds like these to send to you in time to test before you return home. I had planned to just used the current hit compound and add in amide or amine linkers like those shown below and then vary the bits in red. It might give us an idea of whether there is any mileage in them. The students have been in the lab for two days now so will have more to report in a couple of weeks.

image

image

image

MFernflower commented 1 month ago

@OpenSourceMycetoma/corecontrib this is very good since the original hit is basically completely flat in shape - hopefully the work of @P-Rayner can help get series 2 out of flatland!

eloizidou commented 1 month ago

@MFernflower @KlementineJBS @P-Rayner Hi everyone, apologies for the late reply. I think it is worth looking into these analogues. I am thinking from the perspective of interacting with the HDAC enzymes as the additional amide functionality can provide more points of interaction with the Zn ions at the active site of the enzyme. We can also explore a small series of such analogues with the students here however, we won't start experiments until January 2025. @P-Rayner do you have a list of analogues you are making so that I can look for complementary ones?

eloizidou commented 1 week ago

@KlementineJBS Hi Klementine, Whitgift school needs another aminothiazole analogue to synthesise and I can't seem to find the list of desirable molecules on github. Would you mind pointing me to that list or if let me know if you have a specific analogue that you would like to be made? Many thanks.

MFernflower commented 1 week ago

https://github.com/OpenSourceMycetoma/Monthly-zoom-meetings/issues/27#issuecomment-2430577316 @eloizidou

On Wed, Nov 13, 2024, 10:37 AM Erika Loizidou @.***> wrote:

@KlementineJBS https://github.com/KlementineJBS Hi Klementine, Whitgift school needs another aminothiazole analogue to synthesise and I can't seem to find the list of desirable molecules on github. Would you mind pointing me to that list or if let me know if you have a specific analogue that you would like to be made? Many thanks.

— Reply to this email directly, view it on GitHub https://github.com/OpenSourceMycetoma/Series-2-Aminothiazoles/issues/27#issuecomment-2473973650, or unsubscribe https://github.com/notifications/unsubscribe-auth/AAYEWDTYUOVYLRZNGRCF5DT2ANW3ZAVCNFSM6AAAAABJVO7JXKVHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMZDINZTHE3TGNRVGA . You are receiving this because you were mentioned.Message ID: @.*** com>

mattodd commented 1 week ago

@eloizidou also at https://github.com/OpenSourceMycetoma/Series-2-Aminothiazoles/wiki/Overall-summary

eloizidou commented 1 week ago

Great thank you! I can give this molecule to Whitgift, starting material is available and reasonably priced. @.*** image

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: MFernflower @.> Sent: 13 November 2024 15:50 To: OpenSourceMycetoma/Series-2-Aminothiazoles @.> Cc: Loizidou, Erika @.>; Mention @.> Subject: Re: [OpenSourceMycetoma/Series-2-Aminothiazoles] Aminothiazole analogues synthesized by Whitgift school 2024 (Issue #27)

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https://github.com/OpenSourceMycetoma/Monthly-zoom-meetings/issues/27#issuecomment-2430577316 @eloizidou

On Wed, Nov 13, 2024, 10:37 AM Erika Loizidou @.***> wrote:

@KlementineJBS https://github.com/KlementineJBS Hi Klementine, Whitgift school needs another aminothiazole analogue to synthesise and I can't seem to find the list of desirable molecules on github. Would you mind pointing me to that list or if let me know if you have a specific analogue that you would like to be made? Many thanks.

— Reply to this email directly, view it on GitHub https://github.com/OpenSourceMycetoma/Series-2-Aminothiazoles/issues/27#issuecomment-2473973650, or unsubscribe https://github.com/notifications/unsubscribe-auth/AAYEWDTYUOVYLRZNGRCF5DT2ANW3ZAVCNFSM6AAAAABJVO7JXKVHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMZDINZTHE3TGNRVGA . You are receiving this because you were mentioned.Message ID: @.*** com>

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