Aminosteroids from Buxaceae and Apocynaceae Plants as Antiprotozoal Agents: Structural Diversity and Structure–Activity Relationships
- 1University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, PharmaCampus, Corrensstrasse 48, D-48149 Münster, Germany
- 2Swiss Tropical and Public Health Institute (Swiss TPH), Kreuzstrasse 2, CH-4123 Allschwil, Switzerland
- 3University of Basel, Petersplatz 1, CH-4003 Basel, Switzerland
Abstract
As part of our search for new natural chemicals with bioactivity against protozoan pathogens, we have previously reported on the isolation, identification and antiprotozoal activity of over 100 alkaloids with an aminosteroid or related scaffold. We have now investigated the hypothesis that these chemically related compounds also share common mechanisms of action regarding their activity against Trypanosoma brucei rhodesiense (human East African trypanosomiasis) and Plasmodium falciparum (tropical malaria). Furthermore, their cytotoxic activity against mammalian cells (L6 rat skeletal myoblasts) was also included in the investigation. We found that mammalian cytotoxicity is generally lower and there is only a low degree of mutual correlation between the susceptibility of the two parasites and mammalian cells to the compounds’ toxic effects. With the molecular targets being unknown, the 3D-QSAR study was conducted using the Open3Dqsar software. The resulting models show the main structural features influencing the different biological effects. They indicate that indeed related molecular targets underly the cytotoxic, antitrypanosomal and antiplasmodial activity based on structural determinants sufficiently different enough to warrant a significant level of parasite-selectivity. The results of this study offer structural explanations for the observed differences in aminosteroids’ action against the mentioned pathogens and provide a starting point for optimization and simplification of the natural structures towards leads for antiprotozoal drug development.
Related
- The complete mitochondrial genome of Apocynum venetum: a high-quality reference assembly for comparative genomics in Apocynaceae
- Structural diversity of human urinary N-glycans revealed by reversed-phase LC/MS/MS toward a resource for biomarker discovery
- DNA Barcoding and Untargeted Metabolomics Reveal Phylogenetic and Chemotaxonomic Relationships Among 11 Ferula Species from Xinjiang, China
- Design, Amino-Acid-Derived Analogues of FTY-720 and OSU-2S as PP2A Activators: Structure-Activity Relationships and Identification of Lead Compound XML-3D
- Soybean paste functional peptides: Fermentation-driven formation, characterization, classification, structure-activity relationships, and multi-omics insights.
BibTeX
@article{mukavi2026aminosteroids,
title = {{Aminosteroids from Buxaceae and Apocynaceae Plants as Antiprotozoal Agents: Structural Diversity and Structure–Activity Relationships}},
author = {Justus W. Mukavi and Lizanne Schäfer and Lara U. Szabó and Charles O. Nnadi and Julia B. Althaus and Pascal Mäser and Thomas J. Schmidt},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219999},
url = {https://www.mdpi.com/1422-0067/27/21/9999},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Aminosteroids from Buxaceae and Apocynaceae Plants as Antiprotozoal Agents: Structural Diversity and Structure–Activity Relationships
AU - Justus W. Mukavi
AU - Lizanne Schäfer
AU - Lara U. Szabó
AU - Charles O. Nnadi
AU - Julia B. Althaus
AU - Pascal Mäser
AU - Thomas J. Schmidt
PY - 2026
DA - 2026/11/08
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219999
UR - https://www.mdpi.com/1422-0067/27/21/9999
AB - As part of our search for new natural chemicals with bioactivity against protozoan pathogens, we have previously reported on the isolation, identification and antiprotozoal activity of over 100 alkaloids with an aminosteroid or related scaffold. We have now investigated the hypothesis that these chemically related compounds also share common mechanisms of action regarding their activity against Trypanosoma brucei rhodesiense (human East African trypanosomiasis) and Plasmodium falciparum (tropical malaria). Furthermore, their cytotoxic activity against mammalian cells (L6 rat skeletal myoblasts) was also included in the investigation. We found that mammalian cytotoxicity is generally lower and there is only a low degree of mutual correlation between the susceptibility of the two parasites and mammalian cells to the compounds’ toxic effects. With the molecular targets being unknown, the 3D-QSAR study was conducted using the Open3Dqsar software. The resulting models show the main structural features influencing the different biological effects. They indicate that indeed related molecular targets underly the cytotoxic, antitrypanosomal and antiplasmodial activity based on structural determinants sufficiently different enough to warrant a significant level of parasite-selectivity. The results of this study offer structural explanations for the observed differences in aminosteroids’ action against the mentioned pathogens and provide a starting point for optimization and simplification of the natural structures towards leads for antiprotozoal drug development.
SN - 1422-0067
ER -