Medium-Ring Keto Bislactams with Antischistosomal Activity
We discovered medium-ring keto bislactams as a new antischistosomal chemotype. The ketone functional group and isoindolinone substructure were required for high antischistosomal activity. Aryl substitution with EWG functional groups decreased the chemical stability. These compounds were relatively polar with the measured LogD<sub>7.4</sub> values ranging from <0 to 2.4, had kinetic aqueous solubilities between 40 and >320 μM, and had relatively low cytotoxicities with IC<sub>50s</sub> ranging from 52 to >390 μM. We identified two compounds with IC<sub>50</sub> values < 5 μM against ex vivo<i>Schistosoma mansoni</i> (<i>S. mansoni</i>).
Authors
- Jonathan L. Vennerstrom (ORCID: https://orcid.org/0000-0003-0075-2336)
- Cécile Häberli (ORCID: https://orcid.org/0000-0002-1282-8070)
- Kasiram Katneni
- Derek A. Leas (ORCID: https://orcid.org/0000-0002-0190-543X)
- Yuxiang Dong (ORCID: https://orcid.org/0000-0003-1412-3178)
- Rongguo Ren (ORCID: https://orcid.org/0000-0002-1738-1212)
- Susan A. Charman (ORCID: https://orcid.org/0000-0003-1753-8213)
- Marcel Kaiser (ORCID: https://orcid.org/0000-0003-1785-7302)
- Monica Cal (ORCID: https://orcid.org/0009-0007-9959-9891)
- Gong Chen (ORCID: https://orcid.org/0000-0002-5067-9889)
- Jennifer Keiser
Institutions
- Nebraska Medical Center (US)
- Swiss Tropical and Public Health Institute (CH)
- University of Basel (CH)
- Monash University (AU)
- University of Nebraska Medical Center (US)
Publication Details
- Journal
- Journal of Medicinal Chemistry
- Published
- 2024-10-08
- DOI
- https://doi.org/10.1021/acs.jmedchem.4c01532
- Citations
- 3
- Primary Topic
- Phenothiazines and Benzothiazines Synthesis and Activities
- Type
- article
- Field-Weighted Citation Impact
- 0.70
Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- National Institute of Allergy and Infectious Diseases