Sponsor
We gratefully acknowledge the financial support provided by the National Institutes of Health (NIH) through grants AI177660, AI152220, and AI153100 to C.B.M laboratory, which enabled this research. We also thank our colleagues and collaborators for their valuable insights and technical assistance throughout the study. Synthesis of acridone compounds was supported by the NIH/NIAID (award AI158533), DOD/PRMRP (award W81XWH2210494), and VA BLRD (award 1I01BX005674).
Published In
Antimicrobial Agents and Chemotherapy
Document Type
Article
Publication Date
4-27-2026
Subjects
Human babesiosis, acridones, B. microti, B. duncani, B. divergens Rouen87, drug discovery
Abstract
Human babesiosis is an emerging tick-borne disease caused by Babesia parasites, most notably Babesia microti and Babesia duncani in North America and Babesia divergens in Europe. Infections can be severe or persistent or relapse despite treatment, and current therapeutic options remain limited, underscoring the urgent need for new and effective treatment options. Acridone derivatives originally developed as potent antimalarial agents against multiple life cycle stages of the malaria parasites were evaluated for their antibabesial activity using continuous in vitro culture systems of B. duncani and B. divergens. Lead candidates were assessed for selectivity against human cell lines to establish preliminary safety profiles, and select compounds were further advanced into preliminary in vivo efficacy studies using murine models of B. duncani and B. microti babesiosis to assess their therapeutic potential. A set of prioritized acridone derivatives demonstrated potent in vitro activity against both B. duncani and B. divergens and displayed favorable selectivity indices relative to human cell lines. However, in vivo evaluation of representative compounds did not achieve parasite clearance in murine models. Structure-activity relationship (SAR) analyses highlight key structural features that are critical for maintaining antibabesial potency and offer guidance for further lead optimization. Acridone derivatives show strong in vitro antibabesial activity and represent promising lead chemotypes for therapeutic development. To advance these candidates, future studies focused on optimizing their pharmacokinetic properties and evaluating synergistic combination regimens will be essential for progressing toward effective treatments for human babesiosis.
Rights
Copyright (c) 2026 The Authors Creative Commons License This work is licensed under a Creative Commons Attribution 4.0 International License.
Locate the Document
DOI
10.1128/aac.00016-26
Persistent Identifier
https://archives.pdx.edu/ds/psu/44676
Citation Details
Vydyam, P., Zhang, E., Pal, A. C., Dodean, R. A., Kancharla, P., Kelly, J. X., & Ben Mamoun, C. (2026). Evaluating acridones as novel therapeutics for human babesiosis. Antimicrobial Agents and Chemotherapy.