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Home > Scientific articles
Oct 2024

Discovery of a series of macrocycles as potent inhibitors of Leishmania Infantum

Journal of Medicinal Chemistry

by Riu F, Ruppitsch LA, Vo DD, Hong RS, Tyagi M, Matheeussen A, Hendrickx S, Poongavanam V, Caljon G, Sheikh AY, Sjö P, Kihlberg H . Journal of Medicinal Chemistry 2024. doi: 10.1021/acs.jmedchem.4c01370

Summary: Macrocycles are prominent among drugs for treatment of infectious disease, with many originating from natural products. The authors of this article report on the discovery of a series of macrocycles structurally related to the natural product hymenocardine. Members of this series were found to inhibit the growth of Plasmodium falciparum, the parasite responsible for most malaria cases, and of four kinetoplastid parasites. Notably, macrocycles more potent than miltefosine, the only oral drug used for the treatment of the neglected tropical disease visceral leishmaniasis, were identified in a phenotypic screen of Leishmania infantum. In vitro profiling indicated their potential for oral administration, but the series will require further optimization to improve solubility and metabolic stability.

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Drug discovery Visceral leishmaniasis

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