Simple Accessible Clemastine Fumarate Analogues as Effective Antileishmanials

Charlton, Rebecca; Escrivani, Douglas; Brown, Christopher; Thota, Niranjan; de Sousa Agostino, Victor; Porta, Exequiel; Avkiran, Timur; Merritt, Andrew T.; Denny, Paul W; Rossi-Bergmann, Bartira; Steel, P. G.

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.

Citation

Charlton, R., Escrivani, D., Brown, C., Thota, N., de Sousa Agostino, V., Porta, E., Avkiran, T., Merritt, A. T., Denny, P. W., Rossi-Bergmann, B., & Steel, P. G. (online). Simple Accessible Clemastine Fumarate Analogues as Effective Antileishmanials. RSC Medicinal Chemistry, https://doi.org/10.1039/d4md01004c

• Journal Article Type: Article
• Acceptance Date: Jan 28, 2025
• Online Publication Date: Jan 31, 2025
• Deposit Date: Feb 4, 2025
• Publicly Available Date: Feb 5, 2025
• Journal: RSC Medicinal Chemistry
• Electronic ISSN: 2632-8682
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1039/d4md01004c
• Public URL: https://durham-repository.worktribe.com/output/3467214