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OpenSourceMycetoma / Series-1-Fenarimols

Open Source Mycetoma's First Series of Molecules
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Possible screen against Balamuthia???? #17

Closed MFernflower closed 4 years ago

MFernflower commented 4 years ago

Update: Dennis Kyle of the University of Georgia is able to screen against all three genera of neurotrophic amoebas so might be of more value should we proceed further with this avenue.

http://outbreaknewstoday.com/naegleria-fowleri-drug-research-with-dennis-kyle-phd-64534/

CYP51 (the target of the fenarimol drug class) does exist in slime molds (E.G Dictyostelium) and in human pathogenic Balamuthia relative Acanthamoeba castellanii

https://www.uniprot.org/uniprot/Q1ZXH9

https://www.nature.com/articles/s41598-017-07495-z

Joseph DeRisi has papers relating to drug screening methods against a slime-mold-like single-celled extremely virulent neuropathogen known as Balamuthia mandrillaris

Perhaps it could be worthwhile to send some good preforming compounds against Madurella mycetomatis to him to assay vs Balamuthia? (Both organisms have an extremely thick wall but balamuthia's wall is made of cellulose or chitosan not chitin)

MFernflower commented 4 years ago

Thoughts on this @mattodd and @fantasy121 - Currently only one drug known to kill Balamuthia - Nitroxoline

Obligatory video of these things eating cells: Https://www.youtube.com/watch?v=B-GfKM759p0

fantasy121 commented 4 years ago

@MFernflower I think that's a good idea. Perhaps we can choose from our current pool of candidates or wait for the next round of biological evaluation when more compounds are synthesised.

MFernflower commented 4 years ago

@fantasy121 We could perhaps send two compounds that did poorly and two that did great against Madurella mycetomatis in vivo to him - provided we have enough for him to run it in triplicate

MFernflower commented 4 years ago

Of-course there's no guarantee of potency vs Balamuthia as it's cell wall is made of cellulose rather than the chitin wall of Madurella

MFernflower commented 4 years ago

@wwjvdsande Ever heard of this organism?

wwjvdsande commented 4 years ago

No, but we can always try.

MFernflower commented 4 years ago

@wwjvdsande One of the more rare infections out there - Again it's more closely related to slime mold than to actual fungi but as you know, mycology traditionally included study of the slime molds!

wwjvdsande commented 4 years ago

That's true, furthermore the CYP51 target was not only found in fungi

MFernflower commented 4 years ago

Going to re-open this issue with more precise information