Abstract
The fenarimol analogue EPL-BS1246 was previously discovered to be potent against Madurella mycetomatis, the causative agent of the neglected tropical disease eumycetoma. Further evaluation of a small set of fenarimol analogues in vivo revealed a correlation between efficacy and the lipophilicity (logD) of the analogues. To explore both this correlation and the series structure-activity relationship (SAR), we have evaluated a total of 185 fenarimol analogues derived from five different daughter chemotypes. Potent (MIC50 < 9 μM) in vitro activity was found for 22 analogues, five of which gave promising results in an in vivo larval survival assay. Again, a trend towards prolonged larval survival (better in vivo activity) was noted in analogues with logD values < 2.5. Insights into the SAR could be gleaned that suggested optimal substituents for the rings forming the fenarimol core.
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Supporting Information
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Experimental protocols and data for compounds and assays
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Open Source Mycetoma
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Open Source Mycetoma (MycetOS) is an open source drug discovery consortium. Activities are coordinated on Github, and the relevant repository for this project is Number 1, linked above. All data and ideas are freely shared, anyone may participate and no patents will be taken.
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