Simple accessible clemastine fumarate analogues as effective antileishmanials
Rebecca L Charlton1,2, Douglas O Escrivani1,2, Christopher Brown1
1Department of Chemistry, Durham University Lower Mountjoy, South Rd Durham DH1 3LE UK p.g.steel@durham.ac.uk.
Abstract:
Current therapeutic options for leishmaniasis are severely limited, highlighting an urgent need to develop more effective and less toxic drugs to combat a major global public health challenge. Clemastine fumarate displays good levels of antileishmanial efficacy, but further optimisation is challenged by its difficult synthesis. Here, we demonstrate that simple N-linked analogues are easier to access, can exhibit higher selectivity and show comparable efficacy in a mouse model of Leishmania amazonensis infection.
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