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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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Monthly Mycetoma Meeting 29th August 2023 #10

Open mattodd opened 1 year ago

mattodd commented 1 year ago

Time: Aug 29th (12 noon UK, 1pm EU, 9pm 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: #7 Recording: here Present: Apologies: @mattodd

AGENDA

Series 1 - Fenarimols

Final Molecules/SAR Gaps

@fantasy121 completed the selection of Epichem molecules, and the next step is to get them to Wendy.

@fantasy121 shared the list of compounds that have been shipped from Sydney to ErasmusMC.

Paper:

MYOS codes to be used for the compounds, to maintain the link between compounds in the paper and compounds in the live project. The codes needed are just the initial integers, not the batch/salt codes etc. Can also remove zeroes for readability, so e.g. MYOS7.

Siderophores:

New transcriptomic data from @wwjvdsande in the galleria grain model showed that siderophores are produced (https://github.com/OpenSourceMycetoma/What-other-molecules-to-screen/issues/10). These siderophores might be used as a trojan horse to get molecules into the grain. Could we couple fenarimols to fungal-relevant siderophores may be to get them in? The idea of the siderophores was of interest and all partners agreed to consider whether this could be done at the different sites. There is also potential relevance to other series.

Series 2 - Aminothiazoles

@KlementineJBS is the corresponding researcher for this project at USyd. @KlementineJBS has updated the Wiki with the compounds successfully synthesised by USyd in June.

UCL Masters student cohort began in late May and has now (late July) finished their synthetic work.

Series 5 - Benzimidazoles

The related oxazoles: Good potencies observed for recent compound batches (e.g. here). These resemble the benzimidazoles which have shown potent in vivo efficacy. Some oxazoles will be tested against Falciformispora senegalensis too. This series will be evaluated in vivo in the new larval season.

Series 6: ketoximes

Latest compound shipment here, to be tested by @MA-Jjingyi.

@dmitrij176 has obtained a crystal structure for one of the isomers of one of the Series 6 compounds. Separated isomers have been sent to @MA-Jjingyi to see whether they have different potencies. @dmitrij176 is now engaged in experiments to evaluate the conditions under which the isomers interconvert.

@bebi78 suggested evaluating different salts of the ketoximes.

Series 3: Tricyclics/Phenothiazines

Misc updates:

DMPK measurements by Dundee. Compound selection taking place in #8.

Bioinformatics: Waleed requested information on which aspect of bioinformatics should be prioritised to work on first. @wwjvdsande corresponded offline with him. This will include a Phylogenetic tree to work out relationships of various species were identified as high priorities so that we can search the literature for closely related species to Mycetoma, and for the potential structures of the drug target, which would enable us to simulate our data/estimation/computational models. In the May meeting @TariqAyub attended from the Qasim group who will advise on what can be done in terms of future contributions.

Minutes

Manuscript writing Paper editing is underway and needs final corrections from Dmitrij and Hung. Wendy has cleared all of the corrections and needs to edit some figures after other project members double check and finalise the correct list of Fenarimols in the paper. Currently there is a mismatch in numbers of analogues between the SI excel file and the the manuscript.

Previously there has been an agreed cut off point of Fenarimols for the paper which means that novel potency data from Series 1 will not be included.

Remaining paper objectives:

Siderophores Wendy has spoken on the subject with Prof Doyle from Ireland. More information on siderophore studies to follow soon.

Series 2 Aminothiazoles Molecules made by UCL MSc cohort (23 entries) have been shipped to Erasmus MC for testing. Same applies for selected Whitgift compound (MYOS_0590_00_01).

Series 5 Benzimidazoles

Oxazoles having good potencies in recent assays remain of high interest to the MycetOS project (as part of Series 5 development).

Remaining objectives on Series 5

Series 6 Ketoximes Third batch of molecules (27 entries) was dispatched to Rotterdam for testing. Isomer interconversion experiments continue (heat, light,acid catalysis).

Misc/AOB @MA-Jjingyi presented toxicity studies results from the latest compound screening performed at Erasmus MC

Molecules which have shown good performance and selected for further in vivo evalutation (in late summer 2023) include:

In the in vivo stage, most compounds will be tested against both M.mycetomatis and F.senegalensis strains.

29082023.MyctOS.meeting.-MA.pptx

AndreaOtago commented 1 year ago

I likely won't join you live in August, however a very early answer to one of the agenda Qs - yes I shipped the 2023 CHEM 305 benzoxazole compounds to @wwjvdsande in May 2023, and I gave Mycetoma codes to all these compounds in the sheet before sending. We do OSN synthesis at Otago once a year in April-May, so you have all our new 2023 compounds :)

JuliaSarju commented 1 year ago

Hi everyone,

Update from the University of York Student Project. Our student group made great progress and synthesized 10 series 2 compounds and obtained 3 crystal XRD structures. They uploaded their data to the electronic notebook and prepared a poster https://drive.google.com/file/d/11jWPCi1kvc6fg-Ur10j4ThAt3Rok90Xp/view?usp=sharing summarising their work. The compounds need further purification, we probably don't have the capacity to purify them at the moment as we are gearing up for delivering a new reformed course in September. We all really enjoyed working on this project!

We also plan to facilitate a group BSc project to run between September and April (2 days a week) and would really like to continue contributing to the Open Source Pharma Projects. Are there particular areas it would be better for us to focus on for this longer project?

I have trouble attending meetings on Tuesdays as I don't have childcare, but I'll keep a close eye on the discussion threads.

Best wishes, Julia Dr Julia Sarju FHEA , [image: A button with "Hear my name" text for name playback in email signature] https://www.name-coach.com/julia-sarju She/Her Lecturer in Chemistry, Year One Leader, and Chemistry Disability Contact The University of York

UG + PG Chemistry Students: Do you have experiences of inequalities in chemistry education that you want to share with chemistry instructors? Are there actions you would like chemistry departments to take? Add your voice and take part in this RSC Diversity and Inclusion project: Listening to Inequalities in Chemistry Education https://docs.google.com/forms/d/e/1FAIpQLSfF-KSH-VXQOb55kLV_URwZkZVHB32QVM5TdapgSmEtJ3nTWQ/viewform?usp=sf_link

Join the Student Disability Forum Mailing List https://docs.google.com/forms/d/e/1FAIpQLSejLDEYk84XxYXmFQmWphP0At3d0rjbIw_xrgVwS9hOAK7zRw/viewform

On Tue, 25 Jul 2023 at 23:38, MFernflower @.***> wrote:

update on series 3 is here

OpenSourceMycetoma/Series-3-Phenothiazines#6 https://github.com/OpenSourceMycetoma/Series-3-Phenothiazines/issues/6

@OpenSourceMycetoma/corecontrib https://github.com/orgs/OpenSourceMycetoma/teams/corecontrib

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MFernflower commented 1 year ago

@JuliaSarju perhaps if @mattodd does not have more pressing compounds you and your students could take a stab at making some series 3 compounds? some ideas are in here: https://github.com/OpenSourceMycetoma/Series-3-Phenothiazines/issues/6

JuliaSarju commented 1 year ago

@MFernflower Those look really interesting! Dr Julia Sarju FHEA , [image: A button with "Hear my name" text for name playback in email signature] https://www.name-coach.com/julia-sarju She/Her Lecturer in Chemistry, Year One Leader, and Chemistry Disability Contact The University of York

UG + PG Chemistry Students: Do you have experiences of inequalities in chemistry education that you want to share with chemistry instructors? Are there actions you would like chemistry departments to take? Add your voice and take part in this RSC Diversity and Inclusion project: Listening to Inequalities in Chemistry Education https://docs.google.com/forms/d/e/1FAIpQLSfF-KSH-VXQOb55kLV_URwZkZVHB32QVM5TdapgSmEtJ3nTWQ/viewform?usp=sf_link

Join the Student Disability Forum Mailing List https://docs.google.com/forms/d/e/1FAIpQLSejLDEYk84XxYXmFQmWphP0At3d0rjbIw_xrgVwS9hOAK7zRw/viewform

On Wed, 26 Jul 2023 at 12:04, MFernflower @.***> wrote:

@JuliaSarju perhaps if @mattodd doesnt have more pressing compounds you and your students could take a stab at making some series 3 compounds? some ideas are in here:

Message ID: <OpenSourceMycetoma/Monthly-zoom-meetings/issues/10/1651210888@

github.com>

https://github.com/OpenSourceMycetoma/Series-3-Phenothiazines/issues/6

— Reply to this email directly, view it on GitHub https://github.com/OpenSourceMycetoma/Monthly-zoom-meetings/issues/10#issuecomment-1651562211, or unsubscribe https://github.com/notifications/unsubscribe-auth/A4LEEAGSBBONLW7VWHWE273XSD2TXANCNFSM6AAAAAA2W4KGXQ . You are receiving this because you were mentioned.Message ID: @.***>

MFernflower commented 1 year ago

As of the time I am writing this no other lab has time to make the novel phenothiazines (NEU currently does not time to make them but should be able to send a related carbazole series to Wendy for testing)

these are only one or two steps from raw phenothiazine prills and should not be hard provided the students are allowed to use alkyl halides and isovaleric acid anhydride

@JuliaSarju

MFernflower commented 1 year ago

@mattodd @bebi78 I found an interesting compound library: https://www.opnme.com/ - Could not hurt for ask for samples? BI-3231 and crobenetine and BI-2051 seem promising

dmitrij176 commented 1 year ago

@mattodd @wwjvdsande @MA-Jjingyi @fantasy121 does anyone know what happened to the Master List online version. All of the receent compound additions are missing. As if they have been deleted....

MFernflower commented 1 year ago

Strange - I just looked at the master list and it only now has fenarimols?!??! @OpenSourceMycetoma/corecontrib

dmitrij176 commented 1 year ago

Strange - I just looked at the master list and it only now has fenarimols?!??! @OpenSourceMycetoma/corecontrib

Someone must have accidentally deleted it.

MFernflower commented 1 year ago

I just forced a restore - hopefully all is well Dimitri @dmitrij176

mattodd commented 1 year ago

@OpenSourceMycetoma/corecontrib we need an informatics volunteer...

With respect to the Epichem compounds that we hoped to obtain for the fenarimol series, I've managed to make contact with the Epichem team. It's not a simple situation, but for various reasons we have a narrow time window to request molecules. I sent the SCYX codes below to the relevant person, who is being exceptionally helpful, but it turns out it's not easy for them to find the molecules using these codes, and instead what's needed are DNDi or EPL-BS codes. Can someone please look at the codes below and provide the relevant other codes ASAP?

SCYX0001335912 SCYX0001322027 SCYX0001574838 SCYX0001338488 SCYX0001336037 SCYX0001388141 SCYX0001294212 SCYX0001278548 SCYX0001315839 SCYX0001255546 SCYX0001268121

dosreic commented 1 year ago

Codes below in blue

SCYX0001335912 EPL-BS0197

SCYX0001322027 EPL-BS0158 SCYX0001574838 EPL-BS0792 SCYX0001338488 EPL-BS0216 SCYX0001336037 EPL-BS0213 SCYX0001388141 EPL-BS0241 SCYX0001294212 EPL-BS0121 SCYX0001278548 EPL-BS0105 SCYX0001315839 EPL-BS0143 SCYX0001255546 EPL-BS0039 SCYX0001268121 EPL-BS0093

Luiza Cruz, PhD I Drug Discovery Coordinator Drugs for Neglected Diseases initiative (DNDi) Rua São José 70 – Sala 601 - Centro | ZIP 20010020 Rio de Janeiro | Brazil M: +55 37 999072470 | @.**@.> dndi.org

[A picture containing text, clipart Description automatically generated]

De: Mat Todd @.> Enviada em: quinta-feira, 10 de agosto de 2023 06:52 Para: OpenSourceMycetoma/Monthly-zoom-meetings @.> Cc: Luiza Cruz @.>; Mention @.> Assunto: Re: [OpenSourceMycetoma/Monthly-zoom-meetings] Monthly Mycetoma Meeting 29th August 2023 (Issue #10)

@OpenSourceMycetoma/corecontribhttps://github.com/orgs/OpenSourceMycetoma/teams/corecontrib we need an informatics volunteer...

With respect to the Epichem compounds that we hoped to obtain for the fenarimol serieshttps://github.com/OpenSourceMycetoma/Monthly-zoom-meetings/issues/5#issuecomment-1530752314, I've managed to make contact with the Epichem team. It's not a simple situation, but for various reasons we have a narrow time window to request molecules. I sent the SCYX codes below to the relevant person, who is being exceptionally helpful, but it turns out it's not easy for them to find the molecules using these codes, and instead what's needed are DNDi or EPL-BS codes. Can someone please look at the codes below and provide the relevant other codes ASAP?

SCYX0001335912 EPL-BS0197

SCYX0001322027 EPL-BS0158 SCYX0001574838 EPL-BS0792 SCYX0001338488 EPL-BS0216 SCYX0001336037 EPL-BS0213 SCYX0001388141 EPL-BS0241 SCYX0001294212 EPL-BS0121 SCYX0001278548 EPL-BS0105 SCYX0001315839 EPL-BS0143 SCYX0001255546 EPL-BS0039 SCYX0001268121 EPL-BS0093

— Reply to this email directly, view it on GitHubhttps://github.com/OpenSourceMycetoma/Monthly-zoom-meetings/issues/10#issuecomment-1672913606, or unsubscribehttps://github.com/notifications/unsubscribe-auth/A4KDXHUTGAETZIMHBPTXMJTXUSVNXANCNFSM6AAAAAA2W4KGXQ. You are receiving this because you were mentioned.Message ID: @.***>

mattodd commented 1 year ago

Thank you so much @dosreic !

MFernflower commented 1 year ago

@wwjvdsande @bebi78 was the 4-ethyl-closamid and nitroxolin screened yet or are they on waiting list??

MFernflower commented 1 year ago

@lferrins to perhaps post a list of compounds her group has in stock from previous projects about amoeba for possible re-use in mycetoma

https://github.com/OpenSourceMycetoma/Series-3-Phenothiazines/issues/6

JuliaSarju commented 1 year ago

Hi everyone,

I would like to introduce my fab colleague, Dr Peter Rayner (@p-rayner). We will be working with year 3 BSc students who would like to carry out their final project contributing to this OSMycetoma Project.

There is a lot of uncertainty about the number of students at the moment between 6 and 30. We were hoping to run 2-3 groups, where one group looks at the series 3 phenothiazines and the other group/s continues exploring the thiazoles (following on from the mini project students earlier in the year).

We really want these projects to be authentic and to contribute to the wider Mycetoma project. Any guidance and steering would be much appreciated. Unfortunately, neither of us can attend the August group meeting but we will look out for the minutes.

Best wishes, Julia

MFernflower commented 1 year ago

A split between the aminothiazoles and the phenothiazines sounds like a lovely idea as both series are easy to make and have unknown mechanisms of actions

@JuliaSarju @OpenSourceMycetoma/corecontrib

wwjvdsande commented 1 year ago

@OpenSourceMycetoma/corecontrib In my calender invite it was stated that the meeting would be on the 22nd of August. Here it is stated that it is the 29th. I asume it was shifted a bit because of the holidays. I will move the calender invite to match the date of the 29th.

dmitrij176 commented 1 year ago

@OpenSourceMycetoma/corecontrib In my calender invite it was stated that the meeting would be on the 22nd of August. Here it is stated that it is the 29th. I asume it was shifted a bit because of the holidays. I will move the calender invite to match the date of the 29th.

Good day Wendy. Its 29th of August

dmitrij176 commented 1 year ago

@wwjvdsande the bioassay shipment is ready for dispatch today. Will there be anyone to collect it at Rotterdam tomorrow?

wwjvdsande commented 1 year ago

@dmitrij176 yes I will be in and @MA-Jjingyi too

MA-Jjingyi commented 1 year ago

Hi all, the updated results show in the slides, please check. 29082023 MyctOS meeting -MA.pptx

wwjvdsande commented 1 year ago

@OpenSourceMycetoma/corecontrib prof Sean doyle has shipped a fluorescent labled siderophore. Mickey Konings from our lab will test it out.

wwjvdsande commented 1 year ago

@dmitrij176 @fantasy121 is any of you currently working on the fenarimol manuscript? If not, can I do the ref check for the biological part of the manuscript. @mattodd noted that the references have shifted so I need to update that.

dmitrij176 commented 1 year ago

@dmitrij176 @fantasy121 is any of you currently working on the fenarimol manuscript? If not, can I do the ref check for the biological part of the manuscript. @mattodd noted that the references have shifted so I need to update that.

I have some remaining corrections to add. So does Hung I think. But it should be fine as long as we all edit via Word synchronized with Dropbox. Do you have this option @wwjvdsande?

wwjvdsande commented 1 year ago

@dmitrij176 @fantasy121 I'm using that now. I have created a new version called 28 august. I'm just checking the things which need to be done on our side and will replace the references with PMID numbers for now. The one who will submit will need to make an offline copy of it and has to add the references in a reference program such as endnote just before submission. I think that is why it went wrong. I used endnote but when the manuscript was transferred to dropbox the links were messed up.

wwjvdsande commented 1 year ago

@OpenSourceMycetoma/corecontrib is somebody else now working in the paper too? It keeps asking me to open a new version

memm0740 commented 1 year ago

Hi All, I won't be attending the meeting, so I have linked some slides which outline my synthesis progress. I am still trying to synthesise the lead compound in a relatively safe way. I believe I am close to achieving this.

MycetOS 29th Aug meeting.pptx

I have found a few groups in China and Russia that seem to have made the lead compound but was advised to not email them. I will continue looking into finding other groups that have made final compounds or intermediates.

Lastly Klementine and I are still working on entering all of the mycetoma compounds from @rohandavis. We are about half way.

Link to ELN- https://github.com/memm0740/ELN_USYD_Honours

wwjvdsande commented 1 year ago

@fantasy121 @mattodd @dmitrij176 for the paper: I added the missing values as calculated by @dosreic to the master file and the fixed supplementary database and reran the statistics. They are already included in the manuscript. The supplementary excell sheet is now also located in the dropbox.

bebi78 commented 1 year ago

@OpenSourceMycetoma/corecontrib Dear all, I launched a new special issue about antifungals in IJMS (Q1 open access journal) with the topic "Antifungal Drug Discovery: Progresses, Challenges, Opportunities" (see link). 50% APC discounts are available, for eminent researchers full waivers can also be provided. Let me know if there is interest, submission deadline is end of February 2024. @dmitrij176 Maybe your ketoximes might become a suitable contribution?

https://www.mdpi.com/journal/ijms/special_issues/9QZD5S87RF

dmitrij176 commented 1 year ago

Thank you for the invitation @bebi78. Will discuss this with Professor Todd.

bebi78 commented 1 year ago

@dmitrij176 Have you discussed a possible contribution to the special issue with @mattodd ?

dmitrij176 commented 1 year ago

Good day Bernard. Mat was on holiday. Meeting him on Friday. Will let you know as soon as possible.

bebi78 commented 1 year ago

Thanks @dmitrij176 . I talked to colleagues of the journal and I can provide a full waiver, 100% discount on APC, in case of paper acceptance (peer-review pending). Various very interesting scientists from Germany, France, USA and South America have already confirmed to contribute to this special issue.

bebi78 commented 1 year ago

@mattodd @dmitrij176 @wwjvdsande Hello, I sent you the official invitations (one for Mat and one for Wendy) with the available 100% APC discounts for the mentioned antifungals special issue in IJMS. I just have a request. I would need your proforma acceptance of my invitations for you, then I can reserve the full waivers for you. Just send me an email about it.

dmitrij176 commented 1 year ago

Thank you Bernard. Professor Todd(@mattodd) would you be so kind to send that email please. Thank you in advance.