Kronopolitides A–F, a family of 36-membered polyol macrolides with antiparasitic activity against Chagas disease

by Pérez-Bonilla M, Sánchez-Hidalgo M, González I, Martín J, Tormo JR, Cho A, Byun SY, Shum D, Ioset J-R, Reyes F, Genilloud O. Journal of Natural Products 2025. doi: 10.1021/acs.jnatprod.5c01249

Summary: The authors of this manuscript describe a joint effort between Fundación Medina, Institut Pasteur Korea, and DNDi to explore the chemical diversity of microbial natural product libraries and identify novel bioactive compounds against Leishmania donovani and Trypanosoma cruzi. Six new 36-membered polyol macrolides active against T. cruzi were isolated from an extract of Streptomyces kronopolitis and identified using a high-throughput parasite cell-based phenotypic imaging platform. These ‘kronopolitides’ have shown potent antiparasitic activity against T. cruzi (IC₅₀ = 0.10–1.49 μM) and moderate to low activity against L. donovani (IC₅₀ = 0.84–9.25 μM). Kronopolitides could be promising targets for genetic modifications that could lead to the generation of potent bioactive analogues with structural modifications associated with an improvement of activity.