Antifungal Plant Extracts from Nigeria

[bebi78]

The study of antifungal plant extracts from two research groups in Nigeria (Dr. Ogaji, University of Jos; Dr. Nweze, University of Nigeria) will be discussed in this issue.

[MFernflower]

@bebi78 Do we have a list of species?

[mattodd]

I believe @nwezemeka is now invited and part of the group, so we can communicate directly here. Awaiting Dr Ogaji?

It'd be very useful, if someone had some time, to edit the labels (on the right) to better reflect what we need. Some good ones are in the Fenarimol repo.

Also remember that the aim of all Issues is to discuss and then resolve something, e.g. make a decision, take an action, update the wiki. Here I think we'd like to establish the nature of the extracts and whether they can be screened by @wwjvdsande. If we go ahead, please update the wiki before closing, with a link back to this issue.

Very good to have new contributors!

[bebi78]

@nwezemeka Maybe you can make a short list of possible plant extracts you might provide for the project? I wonder if @wwjvdsande has access to the Scedosporium strains, you have used for antifungal testing, and how far these fungi are relevant for eumycetoma disease. @mattod Dr. Ogaji told me that he and his PhD student will sign up soon.

[wwjvdsande]

@bebi78 @nwezemeka @mattodd at the moment we are full in the larvae season and the compounds we need to screen are piling up. I therefore would suggest that when we screen the compounds we will do so after the larvae season ended, in the winter. @MA-Jjingyi will not be able to do this all at the same time. Scedosporium boydii is one of the main causative agents of white grain mycetoma. However we don't come across it very much here. For MycetOS we so-far have mainly focussed on Madurella mycetomatis, we did screen a few other black grain mycetoma causative agents but not the white grain causative agents.

[bebi78]

@mattodd @wwjvdsande @bendndi Is there the possibility that DNDi can cover the shipping costs of the samples of @nwezemeka from Nigeria to Rotterdam next winter? In addition, @nwezemeka can carry out antifungal testing using the pathogenic fungal strains his mycology group in Nigeria is interested in, such as drug-resistant Candida or maybe also Scedosporium species. Might be of relevance for the most active new fenarimol derivatives, for example, would add to Wendy's antifungal results and could be a relief for Wendy. @wwjvdsande Can it be that melanin biosynthesis does not play a role as antifungal target for the white grain fungi?

[wwjvdsande]

@bebi78 @nwezemeka @mattodd I think it is a good idea if @nwezemeka can test against candida and scedosporium species. For white grain mycetoma melanin should not be a bariere as it is not present inside the grain. however in some species there is still a cement like material so other components of that layer could influence the penetration of antifungal agents. Problem is that the cement material is not really studied so the exact nature is not known.

[bebi78]

@wwjvdsande OK. Have you ever tried Clostridium histolyticum Collagenase to break the collagen fibers, in combi with an antifungal drug?

[wwjvdsande]

@bebi78 in vitro the collagen is not a problem so we never tried it in vitro. In vivo it could be that breaking down collagen in general would cause additional problem. The collagen is not only found surrounding the grain it is found in different places as well. I think that doxycylcline might be a better option as it has been used safely as an antibiotic but also to interfere with collagen remoddeling. Doxycycline has been tested in MycetOS and has itself no anti-madurella activity. However if it would enhance the survival of the larvae than it would indeed interfere with the collagen layer surrounding the grain. it is still on our to do list however at the moment we first would like to finish the compounds we needed to screen for this larvae season.

[bebi78]

@wwjvdsande Yes, I know that human MMPs can cause much harm, especially in cancers. We are designing anticancer drugs which downregulate MMP2 and 9 in tumors. But it is a bacterial collagenase approved as Xiapex for the therapy of hand fibrotic tissues in Morbus Dupuytren. A disadvantage of this collagenase compared to doxycycline might surely be its price and protein stability/storage conditions, and that the Swedish provider stopped production of the drug in 2020 because of commercial reasons.

[wwjvdsande]

@bebi78 @mattodd that could be worthwile. Another thing I stumbled upon in our transcriptomic study are siderophores. During infection M. mycetomatis secretes them to obtain iron from the host. For Aspergillus and some bacterial species they use them as trojan horses. We could try that as well to get may be some of the azoles or fenarimols in. The ones which currently have potent in vitro activity but no in vivo efficacy for instance. However I'm not sure if it is possible to make this siderophore synthetically. For aspergillus they isolate it from the culture media. Madurella produces fusarinine C. For aspergillus that is also the molecule they modify to couple antifungal agents to it.

[bebi78]

@wwjvdsande @mattodd Yes, our network here (Bayreuth, Stuttgart, Braunschweig) is doing some research in the field of siderophores, but mainly for bacterial targeting (https://onlinelibrary.wiley.com/doi/10.1002/anie.201701586). It is possible to prepare such siderophores and to make conjugates with antibiotics. My former colleague attached penicillin to a mixed hydroxamate/catechol siderophore (compound 70 in the review). In terms of collagen inhibitors, the asthma drug and simple cinnamide tranilast might also be an alternative to doxycycline.

[bebi78]

@dosreic Is it possible that DNDi can cover the shipment costs (from Nigeria to Rotterdam) of antifungal plant extracts from @nwezemeka and Dr. Ogaji early next year?

[bebi78]

@mattodd @wwjvdsande @MFernflower I received mails from two colleagues, Dr. Ait Itto of the Cadi Ayyat University in Morocco, and Dr. Miller Crotti from Sao Paulo, who showed interest in MycetOS and would like to share some of their compounds for testing vs eumycetoma (see their researchgate profiles below). Dr. Ait Itto is working on bioactive terpenes modified with heterocycles. Dr. Miller Crotti can provide new dihydropyridines and is also working on synthetic cinnamaldehyde and cinnamyl alcohol derivatives at the moment. https://www.researchgate.net/profile/Moulay-Ait-Itto https://www.researchgate.net/profile/Antonio-Eduardo-Crotti

[bebi78]

@wwjvdsande @MA-Jjingyi Dr. Ikoni asked if there are already results for the Nigerian plant extract samples he sent earlier this year.

[wwjvdsande]

@bebi78 do you have the myos codes? That makes it easier for us to locate the results

[bebi78]

@wwjvdsande @MA-Jjingyi Sorry, I made no codes and did not add them to the excel list, because the extracts are complex mixtures of plant components, no defined compounds like fenarimols etc. They need to be tested with % or µg/ml concentration units.

[MFernflower]

Perhaps they need to be retested like the perfume chemicals? @bebi78

On Tue, Nov 21, 2023, 1:05 PM bebi78 @.***> wrote:

@wwjvdsande https://github.com/wwjvdsande @MA-Jjingyi https://github.com/MA-Jjingyi Sorry, I made no codes and did not add them to the excel list, because the extracts are complex mixtures of plant components, no defined compounds like fenarimols etc. They need to be tested with % or µg/ml concentration units.

— Reply to this email directly, view it on GitHub https://github.com/OpenSourceMycetoma/Adjuvant-Screen/issues/2#issuecomment-1821409570, or unsubscribe https://github.com/notifications/unsubscribe-auth/AAYEWDXHZPGDAND4K6J3NWTYFTUQJAVCNFSM5ZI7BMCKU5DIOJSWCZC7NNSXTN2JONZXKZKDN5WW2ZLOOQ5TCOBSGE2DAOJVG4YA . You are receiving this because you were mentioned.Message ID: @.***>

[nwezemeka]

@wwjvdsande please how do we send over our extracts from Nigeria?

On Tue, Nov 21, 2023 at 10:30 AM MFernflower @.***> wrote:

Perhaps they need to be retested like the perfume chemicals? @bebi78

On Tue, Nov 21, 2023, 1:05 PM bebi78 @.***> wrote:

@wwjvdsande https://github.com/wwjvdsande @MA-Jjingyi https://github.com/MA-Jjingyi Sorry, I made no codes and did not add them to the excel list, because the extracts are complex mixtures of plant components, no defined compounds like fenarimols etc. They need to be tested with % or µg/ml concentration units.

— Reply to this email directly, view it on GitHub < https://github.com/OpenSourceMycetoma/Adjuvant-Screen/issues/2#issuecomment-1821409570>,

or unsubscribe < https://github.com/notifications/unsubscribe-auth/AAYEWDXHZPGDAND4K6J3NWTYFTUQJAVCNFSM5ZI7BMCKU5DIOJSWCZC7NNSXTN2JONZXKZKDN5WW2ZLOOQ5TCOBSGE2DAOJVG4YA>

. You are receiving this because you were mentioned.Message ID: @.***>

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--

Prof Emeka I Nweze., MSc, PhD (Nig)., AIMLS (MLSCN), MPH (Cleveland State)

Department of Microbiology AND

Dean

Faculty of Biological Sciences

University of Nigeria, Nsukka

Email: @.***

Editor-in-Chief

Journal of Biological Research and Biotechnology (Bio-Research)

2018-2023

Faculty of Biological Sciences

University of Nigeria, Nsukka

Website: http://www.bioresearch.com.ng/

Free access to all previously published articles here: https://www.ajol.info/index.php/br/issue/archive

[bebi78]

@dosreic Maybe DNDi can cover the shipping costs of the new extracts from @nwezemeka