Compounds from a New Contributor

[mattodd]

Hi all - @bebi78 has joined the project and is offering to ship two molecules to you, @wwjvdsande, for in vitro evaluation if that is OK? The fenarimol-atovaquone hybrids are as follows:

O=C1C(O)=C(C(C2=CC=CN=C2)N3CCN(C(OCC)=O)CC3)C(C4=CC=CC=C41)=O O=C1C(O)=C(C(C2=CC=CN=C2)N3CCN(C(OC(C)(C)C)=O)CC3)C(C4=CC=CC=C41)=O

If this is fine, @dmitrij176 can you please add these two molecules to the Master List and generate MyOS codes? (@bebi78 this is an important part of molecule tracking, obviously).

Wendy please indicate amount needed (either DMSO solution amount/conc, or dry mass accurately weighed) and whether there is a preferred shipping address?

[wwjvdsande]

@mattodd @bebi78 of course we would be willing to screen these. We usually start with a 10 mM starting solution in DMSO to be able to screen a 100 uM concentration in M. mycetomatis. So either 50 ul of this concentration in DMSO or a solid compound of 2-3 mg would be OK.

It can be shipped to:

Department of Medical Microbiology and Infectious Diseases ErasmusMC Medical Microbiology and Infectious Diseases T.a.v. Ma Jingyi and Wendy van de Sande Gebouw NB Kamer NB 920 Westzeedijk 353 3015 AA Rotterdam The Netherlands

[bebi78]

@mattodd @wwjvdsande Thanks. 2-3 mg of each compound is no problem. I will send them asap. I watched your presentations from November 2021 on youtube and some of the compound classes discussed by you and Ed Zijlstra fall into my expertise, too. So if you like I can make some more suggestions of possible or proven antifungal compounds (natural products and synthetic compounds) from my lab we might improve together chemically for antimycetoma activity in the coming months, in case you are interested.

[wwjvdsande]

@mattodd @bebi78 of course I would be willing to collaborate on other compounds too. @MA-Jjingyi is our PhD student who currently tests the compounds and she would certainly be able to screen other compound series too. What compound series would you suggest? You might even make it a separate item on the MycetOS github.

[mattodd]

Hi @bebi78 yes here is a good place to ruminate on possible new compounds, and when we start more seriously on a particular motif (e.g. if there start to be physical compounds in that series) then we can start a new repository.

[MFernflower]

Those are interesting compounds but aren't quinones normally ADMET issues @drc007

[bebi78]

@MFernflower Good point. Maybe the approved antiparasitic atovaquone might be a reference drug to judge this.

[bebi78]

@mattodd @wwjvdsande Here is a list of my past and current projects dealing with compounds or compound classes which have shown antifungal activity or which enhanced the activities of antifungals such as azoles:

1. Natural products and their (semi-)synthetic derivatives: Cinnamyl derivatives Garcinol and its derivatives (Semi-)Synthetic curcumin derivatives Pterostilbene and its derivatives Naphthoquinone derivatives of lawsone, plumbagin, juglone Kojic acid derivatives Triterpene derivatives (betulins and glycyrrhetinic acid derivatives) Derivatives of 3,3’-diindolylmethane (DIM)
2. Synthetic compounds: HDAC inhibitors (mainly hydroxamates) Tubulin binders (mainly compounds targeting the colchicine binding site) Ferrocenes including bimetallic compounds (with Au, Ag, Ru, Pt, Pd)

Looking forward to your comments and questions about anyone of these!

[dmitrij176]

Welcome to the MycetOS project @bebi78. I will update the Master List with these two entries.

[bebi78]

@dmitrij176 Thanks a lot! I hope I can get good news from Enamine about the requested dimethylaminoethyl hydroxylamine precursor soon.

[dmitrij176]

@dmitrij176 Thanks a lot! I hope I can get good news from Enamine about the requested dimethylaminoethyl hydroxylamine precursor soon.

Thanks @bebi78 . I will make further updates on Series 6 ketoximes shortly.

[MFernflower]

@bebi78 I had forgotten we did screen a few natural products: https://pubmed.ncbi.nlm.nih.gov/34106933/

As for atovaquone and friends I'm not certain what the results were......

However I think it's worth screening those atovaquone-fenarimol hybrids and I think everyone else agrees

On Mon, Feb 7, 2022, 10:50 AM dmitrij176 @.***> wrote:

Welcome to the MycetOS project @bebi78 https://github.com/bebi78. I will update the Master List with these two entries.

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[bebi78]

@MFernflower @mattodd @wwjvdsande @dmitrij176 Yes, I like that paper. The major components of CIN-102 are cinnamyls. I worked on synthetic cinnamyl derivatives recently. Maybe some chemical modifications of cinnamyls can be done to enhance the activity.

[MFernflower]

@wwjvdsande has a natural product library ever been screened vs the fungus? I know the cinnamon type compounds were recently

Message ID: <OpenSourceMycetoma/Series-1-Fenarimols/issues/69/1031643290@ github.com>

[MFernflower]

"I worked on synthetic cinnamyl derivatives recently." - @bebi78 Do you still have stock left of them? Maybe could ship to @wwjvdsande to see if they might be synergistic with azoles and whatnot

[wwjvdsande]

@bebi78 @MFernflower one of the Sudanese PhD students I collaborate with has made a small library from extracts of endemic plants and screened that but it was only a small library with not more than 30 products. In the past we screened artemisinin, tea tree oil and the synthetic CIN product for septeos. The latter was also screened in the larvae and showed some activity, especially when we tested a low concentration. I would be surely interested to look further into this and we could always test for synergy with azoles as well. In our study into inhibiting Madurella mycetomatis melanin (https://doi.org/10.1093/mmy/myac003) we found out that when we inhibit DHN melanin with tricyclazole, larvae died very quickly, probably due to the formation of juglone as juglone by itself was also very toxic to the larvae. However inhibiting melanin in vivo also enhanced the activity of azoles. I don't know how many compounds are in your libraries and would like to have screened? @MA-Jjingyi was able to miniturize our initial screening assay so that we can perform that now in a 384 wells plate. Did you also looked in combining the synthetic natural derivatives? Most essential oils work due to the synergy of the individual compounds, that might also be something to look into.

[bebi78]

@MFernflower @mattodd @wwjvdsande Yes, I still have them in stock (see attached file). Some of them are conjugates combining the cinnamoyl moiety with other bioactive compounds such as curcuminoids or plumbagin. Of course, they can be also studied in combination with other known antifungal drugs with different modes of action. I would suggest to send you the cinnamoyls listed in the pdf file and two-three compounds of each compound class mentioned above for testing (ca. 20 compounds), and if there are hits we can discuss how to proceed then.

Cinnamyls.pdf

[mattodd]

Very good! If you'd like to ship, and @wwjvdsande is happy to test, then please just list the SMILES for each so that we can enter them into the Master List to aid tracking/reporting via the generation of MyOS codes.

[MFernflower]

@bebi78 @mattodd @wwjvdsande That 20 compound library is a good start since natural product libraries themselves are often quite pricey:

[MFernflower]

@bebi78 can you post a file with all the structures of your semisynthetic compounds?

[bebi78]

@MFernflower Thanks. It is difficult to show all structures of the last years. So I have attached some of my articles and a word file of the most recent derivatives of triterpenes and pterostilbene. semisynthetic.docx

102.CDF.Qassim.reprint.pdf 52.AOC_DIMFc.printed.pdf 58.lawsone.EJMC.2017.pdf 60.JSCS.Lawsone-Fc.print.pdf 66.HDAC.Animacroxam.MCT.pdf 74.HDAC-Tubulin.Oxazole.pdf 75.DIMPF.ChemBiodiv.pdf 85.lawsone.ArchPharm.pdf 94.lawsonepyran.reprint.pdf 99.Garcinol.RNaseH.pdf 100.SF5curc.Qassim.BOC.pdf

[bebi78]

In addition, I found some time today to search for some more natural compounds in our storage (in addition to those mentioned above. We have the following natural products here: Genistein Emodin Usnic acid Gibberelinic acid Cholic acid and Deoxycholic acid Combretastatin A4 Illudin M Several terpenes and steroids Quinine and other Cinchona alkaloids

Further antibiotic: Trimethoprim

[bebi78]

Sorry, I meant gibberellic acid.

[bebi78]

@mattodd @MFernflower @wwjvdsande OK. The package for Wendy will leave our institute tomorrow by UPS. The content is mentioned in the attached files. I will provide the SMILES codes for the compounds on Monday. If you have any questions let me know. mycetoma.list..docx bebi78.MycetOS.022022.docx

[mattodd]

That's fantastic, @bebi78 - lots of samples! When you've a moment, a sheet with your own codes and the SMILES would be very useful. Molecular formulae and weights would also help. We're going to need to assign a bunch of MyOS codes to these, so please do be clear if any are salts.

[wwjvdsande]

@bebi78 @mattodd @MFernflower @wwjvdsande @MA-Jjingyi That is great @bebi78. We will be on the look-out for these compounds. We will screen them first with 100 uM and 25 uM for activity and take it further from there.

[MA-Jjingyi]

@wwjvdsande @bebi78 @mattodd @MFernflower I am looking forward to screening them. when we receive them ,we will let you all know.

[bebi78]

@mattodd @wwjvdsande @MFernflower @MA-Jjingyi Thanks. No problem. I have added the mol weights in brackets to those ´´further natural products´´ in the file with the compound list, the structures can be easily accessed on wikipedia for these known compounds. But I can also provide the structures with chemdraw on Monday if you want (I'm not in the lab until Monday and don't have chemdraw at home). The same for the SMILES codes. In the word file with the compound structures the mol weights are mentioned under the corresponding structures. The UPS tracking number of the package is: 1Z99F7F10495679767

[MFernflower]

@bebi78 if you want something you can use at home you could look into marvinsketch

On Fri, Feb 11, 2022, 5:44 AM bebi78 @.***> wrote:

@mattodd https://github.com/mattodd @wwjvdsande https://github.com/wwjvdsande @MFernflower https://github.com/MFernflower @MA-Jjingyi https://github.com/MA-Jjingyi Thanks. No problem. I have added the mol weights in brackets to those ´´further natural products´´ in the file with the compound list, the structures can be easily accessed on wikipedia for these known compounds. But I can also provide the structures with chemdraw on Monday if you want (I'm not in the lab until Monday and don't have chemdraw at home). The same for the SMILES codes. In the word file with the compound structures the mol weights are mentioned under the corresponding structures. The UPS tracking number of the package is: 1Z99F7F10495679767

— Reply to this email directly, view it on GitHub https://github.com/OpenSourceMycetoma/Series-1-Fenarimols/issues/69#issuecomment-1036073673, or unsubscribe https://github.com/notifications/unsubscribe-auth/AAYEWDRR6IB2WKBI5TCH6YDU2TSA7ANCNFSM5NXP7K6Q . Triage notifications on the go with GitHub Mobile for iOS https://apps.apple.com/app/apple-store/id1477376905?ct=notification-email&mt=8&pt=524675 or Android https://play.google.com/store/apps/details?id=com.github.android&referrer=utm_campaign%3Dnotification-email%26utm_medium%3Demail%26utm_source%3Dgithub.

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[bebi78]

@wwjvdsande @MFernflower @mattodd @MA-Jjingyi I've seen the package was delivered. Here is the compound list with the SMILES codes for each compound:

Anis-Zimt-Pip: 11 mg O=C(N1CCCCC1=O)/C=C/C2=CC=C(OC)C=C2

Anis-Zimt-Pyr: 10 mg O=C(N1CCCC1=O)/C=C/C2=CC=C(OC)C=C2

TMP-Zimt-Pip: 8 mg O=C(N1CCCCC1=O)/C=C/C2=CC(OC)=C(OC)C(OC)=C2

TMP-Zimt-Pyr: 5 mg O=C(N1CCCC1=O)/C=C/C2=CC(OC)=C(OC)C(OC)=C2

Cl-Zimt-Pip: 9 mg O=C(N1CCCCC1=O)/C=C/C2=CC(Cl)=C(OC)C(OC)=C2

Cl-Zimt-Pyr: 5 mg O=C(N1CCCC1=O)/C=C/C2=CC(Cl)=C(OC)C(OC)=C2

Br-Zimt-Pip: 16 mg O=C(N1CCCCC1=O)/C=C/C2=CC(Br)=C(OC)C(OC)=C2

Br-Zimt-Pyr: 2.2 mg O=C(N1CCCC1=O)/C=C/C2=CC(Br)=C(OC)C(OC)=C2

I-Zimt-Pip: 12 mg O=C(N1CCCCC1=O)/C=C/C2=CC(I)=C(OC)C(OC)=C2

I-Zimt-Pyr: 5 mg O=C(N1CCCC1=O)/C=C/C2=CC(I)=C(OC)C(OC)=C2

Garcinol: 44 mg OC([C@]1(CC@@HC/C=C(C)/C)C([C@]2(C(C)(C)C@HC1)C/C=C(C)/C)=O)=C(C(C3=CC=C(O)C(O)=C3)=O)C2=O

Isogarcinol: 10 mg O=C(C1=CC=C(O)C(O)=C1)C(C2=O)=C(OC(C)(C)C@@HC3)[C@@]34C([C@]2(C(C)(C)C@HC4)C/C=C(C)/C)=O

LTK-14: 4 mg O=C(C1=CC=C(OC)C(O)=C1)C(C2=O)=C(OC(C)(C)C@@HC3)[C@@]34C([C@]2(C(C)(C)C@HC4)C/C=C(C)/C)=O

Curcumin: 16 mg O=C(CC(/C=C/C1=CC=C(O)C(OC)=C1)=O)/C=C/C2=CC(OC)=C(O)C=C2

MePip-SF5: 8 mg O=C(/C(CN(C)C/1)=C/C2=CC=C(S(F)(F)(F)(F)F)C=C2)C1=C\C3=CC=C(S(F)(F)(F)(F)F)C=C3

Zimt-DF: 16 mg O=C(/C(CN(C(/C=C/C1=CC=CC=C1)=O)C/2)=C/C3=CC(F)=C(F)C=C3)C2=C\C4=CC=C(F)C(F)=C4

Zimt-DiFiD: 15 mg O=C(/C(CN(C(/C=C/C1=CC=CC=C1)=O)C/2)=C/C3=C(F)C=C(F)C=C3)C2=C\C4=CC=C(F)C=C4F

Pterostilbene: 30 mg OC(C=C1)=CC=C1/C=C/C2=CC(OC)=CC(OC)=C2

Ptero-Hepam: 9 mg ONC(CCCCCCOC(C=C1)=CC=C1/C=C/C2=CC(OC)=CC(OC)=C2)=O

Lawsone: 32 mg O=C1C(O)=CC(C2=CC=CC=C21)=O

2-Methoxy-1,4-naphthoquinone: 11 mg O=C1C(OC)=CC(C2=CC=CC=C21)=O

Law-2py-16: 14 mg O=C1C(O)=C(C(C2=CC=CC=N2)NCCCCCCCCCCCCCCCC)C(C3=CC=CC=C31)=O

Lw-3py: 13 mg O=C1C(OC(N)=C(C#N)C2C3=CC=CN=C3)=C2C(C4=CC=CC=C41)=O

Lw-Br: 12 mg O=C1C(OC(N)=C(C#N)C2C3=CC(OC)=C(OC)C(Br)=C3)=C2C(C4=CC=CC=C41)=O

Juglone: 15 mg O=C1C=CC(C2=C(O)C=CC=C21)=O

5,8-Dihydroxy-1,4-naphthoquinone (Naphthazarin): 13 mg O=C1C=CC(C2=C(O)C=CC(O)=C21)=O

Plu-Zimt: 7 mg O=C1C(C)=C/C(C2=C1C=CC=C2O)=N\NC(/C=C/C3=CC=CC=C3)=O

Law-3py-Etcpipaz: 23 mg O=C1C(O)=C(C(C2=CC=CN=C2)N3CCN(C(OCC)=O)CC3)C(C4=CC=CC=C41)=O

Law-3py-Bocpipaz: 16 mg O=C1C(O)=C(C(C2=CC=CN=C2)N3CCN(C(OC(C)(C)C)=O)CC3)C(C4=CC=CC=C41)=O

Kojic acid: 34 mg O=C1C(O)=COC(CO)=C1

Koji-3py: 12 mg O=C1C(OC(N)=C(C#N)C2C3=CC=CN=C3)=C2OC(CO)=C1

Betulonic acid: 1.8 mg O=C1CC[C@@]2(C)C(CC[C@]3(C)C2CCC4[C@@]3(C)CC[C@]5(C(O)=O)C4C@HCC5)C1(C)C

Betulon-Ru-Cymol: 12 mg O=C1CC[C@@]2(C)C(CC[C@]3(C)C2CCC4[C@@]3(C)CC[C@]5(C(N6C=CN=C6)=O)C4C@HCC5)C1(C)C.CC(C)c7ccc(C)cc7

Bet-Nofu: 19 mg O[C@H]1CC[C@@]2(C)C(CC[C@]3(C)C2CCC4[C@@]3(C)CC[C@]5(C/N=C/C6=CC=C(N+=O)O6)C4C@HCC5)C1(C)C

Bet-NoS: 10 mg O[C@H]1CC[C@@]2(C)C(CC[C@]3(C)C2CCC4[C@@]3(C)CC[C@]5(C/N=C/C6=CC=C(N+=O)S6)C4C@HCC5)C1(C)C

Glycyrrhetinic acid: 10 mg O[C@H]1CC[C@@]2(C)C(CCC@CC3)(C)C4=C5)(C)C2C5=O)C1(C)C

Glycyrrhethin-Nap: 12 mg O[C@H]1CC[C@@]2(C)C(CCC@=O)CC3)(C)C4=C6)(C)C2C6=O)C1(C)C

Glycyrrhetin-PF: 10 mg O[C@H]1CC[C@@]2(C)C(CCC@=O)CC3)(C)C4=C7)(C)C2C7=O)C1(C)C

DIM (3,3’-diindolylmethane): 27 mg C1(CC2=CNC3=C2C=CC=C3)=CNC4=C1C=CC=C4

DIM-PF: 13 mg FC(C(F)=C1F)=C(F)C(F)=C1C(C2=CNC3=C2C=CC=C3)C4=CNC5=C4C=CC=C5

Broxbam: 9 mg BrC1=C(OC)C(OC)=CC(C2=C(C3=CC=C(OC)C(OCCCC(NO)=O)=C3)OC=N2)=C1

Brimamin: 6 mg BrC1=C(OC)C(OC)=CC(C2=C(C3=CC=C(OC)C(N)=C3)N(C)C=N2)=C1

Bcr-3NO: 10 mg NC1=C(C#N)C(C2=CC=CC(N+=O)=C2)C3=C(C(C=CC=C4)=C4C=C3)O1

Chalcone: 14 mg O=C(/C=C/C1=CC=C(OC)C(O)=C1)C2=CC(OC)=C(OC)C(OC)=C2

Anim-Purin: 15 mg CN1C2=NC=NC(N(C)C3=CC=C(OC)C=C3)=C2N=C1

Genistein (M = 270.24 g/mol): 18 mg Oc1ccc(cc1)C\3=C\Oc2cc(O)cc(O)c2C/3=O

Naringin (M = 580.54 g/mol): 63 mg O=C4c5c(O)cc(O[C@@H]2OC@HC@@HC@H[C@H]2O[C@H]1OC@@HC)cc5OC@HC4

Oleandomycin phosphate (M = 785.9 g/mol): 30 mg CC1CC(C(C(O1)OC2C(CC3(CO3)C(=O)C(C(C(C(OC(=O)C(C(C2C)OC4CC(C(C(O4)C)O)OC)C)C)C)O)C)C)O)N(C)C.OP(=O)(O)O

Emodin (M = 270.24 g/mol): 16 mg O=C2c1cc(cc(O)c1C(=O)c3c2cc(O)cc3O)C

(+)-Usnic acid (M = 344.32 g/mol): 80 mg CC1=C(C(=C2C(=C1O)C3(C(=CC(=O)C(C3=O)C(=O)C)O2)C)C(=O)C)O

Gibberellic acid (M = 346.38 g/mol): 14 mg O=C1O[C@@]52\C=C/C@H[C@]1([C@H]5C@H[C@]43[C@H]2CCC@@(C(=C)C3)C4)C

Cholic acid sodium salt (M = 430.6 g/mol): 46 mg CC(CCC(=O)[O-])C1CCC2C1(C(CC3C2C(CC4C3(CCC(C4)O)C)O)O)C.[Na+]

Deoxycholic acid sodium salt (M = 414.6 g/mol): 53 mg CC(CCC(=O)[O-])C1CCC2C1(C(CC3C2CCC4C3(CCC(C4)O)C)O)C.[Na+]

Combretastatin A4 (M = 316.35 g/mol): 19 mg COC1=C(C=C(C=C1)C=CC2=CC(=C(C(=C2)OC)OC)OC)O

Illudin M (M = 248.32 g/mol): 13 mg CC1=C2C(C(C=C2C(=O)C(C13CC3)(C)O)(C)C)O

Quinine hydrobromide (M = 405.33 g/mol): 25 mg COC1=CC2=C(C=CN=C2C=C1)C(C3CC4CCN3CC4C=C)O.Br

Gramicidine D (M = ca. 2000 g/mol): 13 mg CC@@HC(=O)NC@@HC(=O)NC@HC(=O)NC@@HC(=O)NC@@HC(=O)NC@@HC(=O)NC@HC(=O)NC@@HC(=O)NC@HC(=O)NC@@HC(=O)NC@HC(=O)NC@@HC(=O)NCCO)NC(=O)CNC(=O)C@HNC=O

Trimethoprim (M = 290.32 g/mol): 26 mg Nc1nc(N)ncc1Cc(cc2OC)cc(OC)c2OC

[bebi78]

@mattodd Sorry, seems that some longer SMILES codes were truncated during the pasting. Here is the word file with the complete SMILE for every compound. mycetoma.list.MycetOS.docx

[flavioemery]

Hi colleagues, I have some quinones to share with you all. I have some more, but are quite related to those!

[mattodd]

Hi @flavioemery - that's great. I don't think compounds like these have been evaluated previously. Are you happy to test these, too, @wwjvdsande?

@OpenSourceMycetoma/corecontrib - we need some volunteers to manage the addition of the compounds sent by @bebi78 and @flavioemery to the Master List so that they have unique MyOS IDs based on the compound numbering system. Local codes can be added too, but MyOS codes are essential so that we all know which compounds we're talking about.

[dmitrij176]

Hi @flavioemery - that's great. I don't think compounds like these have been evaluated previously. Are you happy to test these, too, @wwjvdsande?

@OpenSourceMycetoma/corecontrib - we need some volunteers to manage the addition of the compounds sent by @bebi78 and @flavioemery to the Master List so that they have unique MyOS IDs based on the compound numbering system. Local codes can be added too, but MyOS codes are essential so that we all know which compounds we're talking about.

Good evening. I am happy to help with this. @flavioemery can you please upload the SMILES codes. @bebi78 list has been published, so I will add these compounds too.

[wwjvdsande]

@flavioemery @mattodd @MA-Jjingyi yes we will screen those too.

[MA-Jjingyi]

@bebi78 @mattodd @wwjvdsande We have received the 51 compounds. Screening plans will be done. thanks.

[flavioemery]

@dmitrij176 Here it is:

O=C1C=C(NC2=CC=CC=C2)C(C3=C1NC(C)(C)NC3=O)=O

O=C4C(O)=C(NC5=CC=C(OC)C=C5)C(C6=C4C=CC=C6)=O

O=C7C(O)=C(NC8=CC(OCCO9)=C9C=C8)C(C%10=C7C=CC=C%10)=O

O=C%11C(Cl)=C(NC%12=CC=CC=C%12Cl)C(C%13=C%11C=CC=C%13)=O

O=C%14C(OS(C(F)(F)F)(=O)=O)=C(NC%15=CC=CC=C%15)C(C%16=C%14C=CC=C%16)=O

O=C%17C(O)=C(C/C=C(C)/C)C(C%18=C%17C=CC=C%18)=O

O=C%19C(O)=C(/C=C/C(C)C)C(C%20=C%19C=CC=C%20)=O

O=C%21C(NC)=C(C/C=C(C)/C)C(C%22=C%21C=CC=C%22)=O

O=C%23C(OS(C)(=O)=O)=C(C/C=C(C)/C)C(C%24=C%23C=CC=C%24)=O

O=C%25C(OS(C%26=CC=C(C)C=C%26)(=O)=O)=C(C/C=C(C)/C)C(C%27=C%25C=CC=C%27)=O

O=C%28C%29=C(C=CC(C)(C)O%29)C(C%30=C%28C=CC=C%30)=O

O=C%31C%32=C(CCC(C)(C)O%32)C(C%33=C%31C=CC=C%33)=O

O=C(C%34=C(C%35=C%36CCC(C)(C)O%35)C=CC=C%34)C%36=O

O=C%37C(O)=C(N%38CCN(C%39=CC=C(N+=O)C=C%39)CC%38)C(C%40=C%37C=CC=C%40)=O

O=C%41C(OC(C)(C#C)C)=CC(C%42=C%41C=CC=C%42)=O

O=C%43C(N=[N+]=[N-])=C(Cl)C(C%44=C%43C=CC=C%44)=O

O=C%45C(Cl)=CC(C%46=C%45C=CC=C%46)=O

O=C(N%47CCN(C(C%48=O)=C(C(C%49=C%48C=CC=C%49)=O)OC(C)=O)CC%47)C

ClCCNC(C%50=O)=C(C(C%51=C%50C=CC=C%51)=O)O

O=C%52C(O)=C(CCC(C)C)C(C%53=C%52C=CC=C%53)=O

O=C%54C(O)=C(NC%55=C(Cl)C=CC=C%55)C(C%56=C%54C=CC=C%56)=O

O=C%57C(O)=C(NC%58=CC(C(F)(F)F)=CC=C%58)C(C%59=C%57C=CC=C%59)=O

O=C%60C(O)=C(NC%61=CC=C(F)C=C%61)C(C%62=C%60C=CC=C%62)=O

O=C%63C(O)=C(NC%64=C(OC)C(OC)=CC=C%64)C(C%65=C%63C=CC=C%65)=O

C=C(O%66)C(C)(C)C%67=C%66C(C%68=C(C%67=O)C=CC=C%68)=O

[bebi78]

@mattodd @MFernflower @wwjvdsande I searched our department for more possible or proven antifungal compounds (natural and synthetic ones) last week and I attached a word file with the compounds I found interesting. Maybe you can have a look and tell me if there is interest in any of them. In addition, I contacted my colleague Dr. Marc Stadler, mycologist of the HZI in Braunschweig, if he has antifungal natural products in stock. He said not yet but he will inform me when he has suitable candidates in future. Last year he started a EU project with the WFBI in Utrecht and others which is intended to identify new bioactive compounds from fungi. He is also working on the taxonomy of Sordariales fungi (attached pdf), maybe of relevance for diagnostics of further eumycetoma fungi.

https://www.helmholtz-hzi.de/en/research/research-topics/anti-infectives/microbial-drugs/marc-stadler/?tx_list_pi1%5Buid%5D=14&tx_list_pi1%5Bmode%5D=42&cHash=acb0f54094f1f42417cee63d4127d064

Noumeur2020_Article_DiketopiperazinesFromBatnamyce.pdf

List.2.MycetOS.docx

[MFernflower]

@bebi78 the list of compounds is pretty interesting lots of essential oil type components and various alkaloids

Do you have chlorpromazine or trifluoperazine to spare Im curious about there antifungal effects and I think Wendy will be willing to screen anything to try and find new leads against this infection

Would be cool if maybe some native plant to the areas where mycetoma is rampant kills the fungus

@wwjvdsande

[bebi78]

@MFernflower @wwjvdsande @mattodd Sorry, I could not find chlorprimazine and trifluoperazine in our database. But chlorprimazine is not expensive and available from common providers. Instead, I have thionine chloride and methylene blue as thiazine derivatives in stock, if these compounds are of interest.

My colleagues of the Qassim University are investigating Arabian medicinal plants for the treatment of protozoal parasites. I will ask them if they agree to provide some interesting plant extracts. One of them is Sudanese and worked in Khartoum before (Medicinal and Aromatic Plants Research Institute, National Center for Research, Khartoum) where he investigated African and, in particular, Sudanese plants. Maybe there are still connections to get more samples for mycetoma testing.

I'm trying to take part in the zoom meeting of the group. Because it is 10 pm here, I have to join the meeting from my home office and hope that the connection will be OK from there. So don't be upset if I disappear from time to time in the middle of the meeting. But next time I could join from the university where there is a better net connection.

[MA-Jjingyi]

@OpenSourceMycetoma/corecontrib - we need some volunteers to manage the addition of the compounds sent by @bebi78 and @flavioemery to the Master List so that they have unique MyOS IDs based on the compound numbering system. Local codes can be added too, but MyOS codes are essential so that we all know which compounds we're talking about.

Good evening. I am happy to help with this. @flavioemery can you please upload the SMILES codes. @bebi78 list has been published, so I will add these compounds too.

Hi, @dmitrij176 .would you like to help we find the MW information of those 51 compounds too? thanks.

[dmitrij176]

@flavioemery could you please reupload the SMILES code for the following compound: O=C%37C(O)=C(N%38CCN(C%39=CC=C(N+=O)C=C%39)CC%38)C(C%40=C%37C=CC=C%40)=O It appears that you inserted a hyperlink and the code is not recognised by ChemDraw. I removed it manually, but want to make sure its the right structure. I think it should be NO2 on benzene.

[bebi78]

@MFernflower @mattodd @wwjvdsande @MA-Jjingyi My cooperation partner, Dr. Waleed S. Koko of the Qassim University in KSA, informed me that his former colleagues in Khartoum may have suitable medicinal plant extracts for free and begs you and Dr. Fahal to contact him and his colleagues. Can be that one or two of the the suggested extracts were already dealt with in Wendy's paper from 2015. So a discussion of the offered extracts might be necessary in order to avoid redundancies. Dr. Koko's email address is: wasyko2002@yahoo.com

[wwjvdsande]

@bebi78 @MFernflower @mattodd @MA-Jjingyi Shereen Omer and prof Sami Khalid are currently testing Sudanese medicinal plants for activity against mycetoma causative agents. It will run it by them as well as it will be indeed a shame if we are running the exact same extracts as they are.

[bebi78]

@wwjvdsande OK, thanks. I wrote Dr. Koko to contact Prof. Khalid in Khartoum.

[flavioemery]

@dmitrij176 that's the correct SMILES code: O=C1C(O)=C(N2CCN(C3=CC=C(N+=O)C=C3)CC2)C(C4=CC=CC=C41)=O

You are correct, it is the nitro (not the nitroso).

I am preparing the samples for you guys. What's the shipping address?

[MFernflower]

@flavioemery

[bebi78]

@wwjvdsande @MA-Jjingyi @MFernflower I have prepared a package with cinnamyls and alkaloids (see attached file). If you want me to add any other compound from my list let me know. Otherwise I will dispatch the compounds on Friday.

@flavioemery Shipping address of Wendy in Rotterdam see above (second comment of Wendy).

Cinnamyl.Alkaloids.docx

[wwjvdsande]

@bebi78 @mattodd I do no the group in Westerdijk too. We already screened one of their early fungal libraries and got 2 or 3 hits. They just purified the compound and we still need to confirm their hit.

[wwjvdsande]

@wwjvdsande @MA-Jjingyi @MFernflower I have prepared a package with cinnamyls and alkaloids (see attached file). If you want me to add any other compound from my list let me know. Otherwise I will dispatch the compounds on Friday.

@flavioemery Shipping address of Wendy in Rotterdam see above (second comment of Wendy).

Cinnamyl.Alkaloids.docx

@bebi78 @MFernflower @mattodd it looks ok to me. May be we screen first and then see which direction we get the most hits? We need to narrow down at some point which series we take to the larval model. Unfortunately if we get a lot of different hits it will be impossible for @MA-Jjingyi to screen everything in the larvae as well. It is quite labour intensive.

[bebi78]

@wwjvdsande @MA-Jjingyi Sure. Only the most promising compounds should advance to animal testing. The package will go out tomorrow by UPS again. I will let you know the tracking number as soon as I get it from UPS.