Refreshing the anti-leishmanial pipeline: synthesis and characterisation of tamoxifen/clemastine hybrid molecules
As a way of overcoming time and financial problems related to the drug development process, repurposing raises as an alternative strategy. Drug repurposing is defined as using drugs aimed for one disease to another disease. During the last decade, for example, tamoxifen, a known anti-breast cancer drug, has been shown to be active against some species of Leishmania. Also, clemastine, a anti-histaminic, has been shown to be a potent anti-leishmanial. Surprisingly, both molecules share similar chemical structure and have been proposed to target the same enzyme, which is exclusive to the parasite and not present in the host.
In this project, our aim is to synthesise chimera molecules based on tamoxifen and clemastine. Once the molecules are designed and obtained, they will be tested against different species of Leishmania, in in vitro and in vivo models, and we will possibly identify their intracellular targets. Finally, we will work on elucidating the mechanism of action of these molecules.
Victor de Sousa Agostino
