Simple accessible clemastine fumarate analogues as effective antileishmanials
Rebecca L. Charlton, Douglas O. Escrivani, Christopher Brown, Niranjan Thota, Victor S. Agostino, Exequiel O. J. Porta, Timur Avkiran, Andrew T. Merritt, Paul W. Denny, Bartira Rossi-Bergmann, Patrick G. Steel
TL;DR
Researchers developed simpler versions of a drug called clemastine fumarate that are easier to make and work well against leishmaniasis.
Contribution
The study introduces simpler N-linked analogues of clemastine fumarate with improved accessibility and selectivity.
Findings
N-linked analogues are easier to synthesize than clemastine fumarate.
The analogues show higher selectivity and comparable efficacy in treating Leishmania amazonensis infection in mice.
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. N-linked analogues of clemastine fumarate afford simpler, more accessible, more selective antileishmanials.
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Taxonomy
TopicsResearch on Leishmaniasis Studies · Chemical synthesis and pharmacological studies · Synthesis and Biological Evaluation