Results of screening

[wwjvdsande]

During her PhD, @MA-Jjingyi has screened the 5631 compound libary from Oncode. From those screenings two compounds were able to prolong larval survival:

Might be interesting hits to look further into.

Both compounds were developed as NF-kB inhibitors, which are not present in fungi. However, they could potentially bind the fungal specific Velvet proteins.

The hits of the oncode library are uploaded in the spreadsheet.

[wwjvdsande]

@mattodd @KlementineJBS @P-Rayner are these compounds may be of interest for the highschool students? Don't know if they are easy to be made of adapted

[mattodd]

@wwjvdsande great you posted these data! Would you be able to add a few words of background to the ReadMe at https://github.com/OpenSourceMycetoma/Oncode-library

Looking at the two structures above, they look small and potentially toxic. Do we have any data on tox? Does the library come with that, if they are known bioactives?

[wwjvdsande]

@mattodd I will try to add the background to the ReadMe. was not able to do it a few hours ago. We did do toxicity testing in the larvae and they were not toxic at the concentration we used. The spreadsheet uploaded was the data we had associated with the library. However, since most of these were also tested in human there should be some tox data. Might not be public available though.

[MFernflower]

One of the hits is close to niclosamide which we have partly looked at in the past - perhaps we should fully launch a series 7 based on niclosamide derivatives?

Tagging @bebi78 because he has expertise in Salicylic acid derivatives

[MFernflower]

https://github.com/OpenSourceMycetoma/Series-7-Salicylanilides

@bebi78

@wwjvdsande

Opened a new area up so discussion can continue

[bebi78]

@MFernflower @mattodd @wwjvdsande There are two antibacterial gold(I) complexes with sulfur ligands derived from BAY-117085 published in 2023 by a group in Rhode Island (see link, open access). Maybe we could ask them for sending a sample.

https://www.frontiersin.org/journals/antibiotics/articles/10.3389/frabi.2023.1179354/full

[bebi78]

@OpenSourceMycetoma/corecontrib NF-kappaB suppressors usually act via inhibition of the NF-kappaB-activating protein kinase IKK. So maybe it is possible to connect this drug class on MycetOS with kinase inhibitor projects? There seem to be some kinases (MpkB, FphA) which regulate fungal velvet activity by phosphorylation. Maybe it can be checked first if these kinases or velvet are expressed in eumycetoma strains.

[bebi78]

@OpenSourceMycetoma/corecontrib We published a review manuscript about the antifungal activities of the well-known NF-kappaB inhibitor and gold-based anti-rheumatic drug auranofin now (see link). It also contains a brief discussion of other antifungal gold complexes, e.g. a Brazilian group reported azole gold complexes.

https://www.mdpi.com/1422-0067/26/16/7909

[bebi78]

@OpenSourceMycetoma/corecontrib The results of the Oncode library screening were published now.

https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkaf369/8267121?searchresult=1