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OpenSourceMycetoma / What-other-molecules-to-screen

Suggestions for New Series for MycetOS
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Clues to MoA for 2-aminothiazoles #14

Open KlementineJBS opened 2 weeks ago

KlementineJBS commented 2 weeks ago

COPIED FROM SERIES 2 WIKI

(We can use this page to elucidate what is likely to be the mechanism of action of these compounds, based on literature for structurally similar compounds. This was described in the 23rd April 2024 Meeting)

Possible biological targets for aminothiazoles:

1) 24C-methyl transferase may be a possible target for this class of molecules. The aminothiazole heterocycle is also featured in abafungin, an antimicrobial agent used for treatment of dermatomycoses, which has been shown to inhibit the enzyme sterol 24C-methyl transferase. (Chemotherapy. 2008 Aug; 54(4): 245–259; doi: 10.1159/000142334)

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abafungin

2) Histone deacetylase may be another target. HDAC inhibitors have been shown to act in synergy with azole antifungal drugs. This is a zinc containing enzyme and inhibitors usually have a metal chelating moiety such as hydroxamate on their structure, but some papers suggest that aminothiazoles may also chelate metals. (Clinical Pharmacology and Therapeutics (1993) 54, 473–475; doi:10.1038/clpt.1993.178; ACS Omega 2021, 6, 33085−33099)

KlementineJBS commented 2 weeks ago

this is being worked on by @eloizidou and her students at UCL