Relationship between nanoscale assembly and cytotoxicity in the piperazine amides of betulinic acid: an in vitro study.
4 affiliations
- 1Department of Chemistry of Natural Compounds, University of Chemistry and Technology in Prague CZ-16628 Prague Czech Republic [email protected].
- 2Institute of Macromolecular Chemistry, Czech Academy of Sciences CZ-16206 Prague Czech Republic.
- 3Laboratory of Growth Regulators, Faculty of Science, Palacký University & Institute of Experimental Botany, Czech Academy of Sciences CZ-77900 Olomouc Czech Republic.
- 4Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences CZ-16610 Prague Czech Republic.
Abstract
Six new piperazine amides of betulinic acid, partly decorated with a glycine unit, were synthesized and purified and their structures were elucidated. This study explored whether relationships could be identified among the molecular structures, nanoscale self-assembly, and cytotoxicity of the synthesized compounds. Because of the limited quantities of the target compounds finally available for the analytical methods, their selection had to be very careful. NMR spectroscopy and mass spectrometry were used to elucidate the molecular structures, while transmission electron microscopy (TEM) was employed to characterize the supramolecular structures formed after dissolution in methanol and water. The target compounds reproducibly displayed several basic morphologies depending on the solvent type (methanol vs. water) and the time in solution (1 h vs. 48 h). Several characteristic morphologies were observed, including cloud-like assemblies, isometric nanoparticles of various sizes, fibrous nanostructures with thicknesses below 10 nm, and combinations of these structures, depending on the compound, solvent, and time in solution. The target compounds (6 and 8), the parent compound (1) and the intermediates (2 and 4) were subjected to cytotoxicity assays in the HeLa and MCF7 cancer cell lines while using normal human fibroblasts (BJ) as the reference cells. Cisplatin (cis-diaminedichloroplatinum(ii), CDDP), a pharmacologically used anticancer agent, was used for comparing the cytotoxicity levels and cytotoxicity profiles of the studied compounds. Compounds 6 and 8 were specifically examined for possible associations between nanoscale self-assembly and cytotoxicity studied in vitro. The results provided initial insights into the complex relationship among the molecular structures, self-assembly, and cytotoxicity of the studied compounds.
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BibTeX
@article{wimmerova2026relationship,
title = {{Relationship between nanoscale assembly and cytotoxicity in the piperazine amides of betulinic acid: an in vitro study.}},
author = {Martina Wimmerová and Miroslav Šlouf and Lucie Rárová and Marie Kvasnicová and David Šaman and Zdeněk Wimmer},
journal = {RSC medicinal chemistry},
year = {2026},
month = sep,
doi = {10.1039/d6md00638h},
url = {https://europepmc.org/article/MED/42835445},
note = {CC BY},
}
RIS
TY - JOUR
TI - Relationship between nanoscale assembly and cytotoxicity in the piperazine amides of betulinic acid: an in vitro study.
AU - Martina Wimmerová
AU - Miroslav Šlouf
AU - Lucie Rárová
AU - Marie Kvasnicová
AU - David Šaman
AU - Zdeněk Wimmer
PY - 2026
DA - 2026/09/08
JO - RSC medicinal chemistry
DO - 10.1039/d6md00638h
UR - https://europepmc.org/article/MED/42835445
AB - Six new piperazine amides of betulinic acid, partly decorated with a glycine unit, were synthesized and purified and their structures were elucidated. This study explored whether relationships could be identified among the molecular structures, nanoscale self-assembly, and cytotoxicity of the synthesized compounds. Because of the limited quantities of the target compounds finally available for the analytical methods, their selection had to be very careful. NMR spectroscopy and mass spectrometry were used to elucidate the molecular structures, while transmission electron microscopy (TEM) was employed to characterize the supramolecular structures formed after dissolution in methanol and water. The target compounds reproducibly displayed several basic morphologies depending on the solvent type (methanol vs. water) and the time in solution (1 h vs. 48 h). Several characteristic morphologies were observed, including cloud-like assemblies, isometric nanoparticles of various sizes, fibrous nanostructures with thicknesses below 10 nm, and combinations of these structures, depending on the compound, solvent, and time in solution. The target compounds (6 and 8), the parent compound (1) and the intermediates (2 and 4) were subjected to cytotoxicity assays in the HeLa and MCF7 cancer cell lines while using normal human fibroblasts (BJ) as the reference cells. Cisplatin (cis-diaminedichloroplatinum(ii), CDDP), a pharmacologically used anticancer agent, was used for comparing the cytotoxicity levels and cytotoxicity profiles of the studied compounds. Compounds 6 and 8 were specifically examined for possible associations between nanoscale self-assembly and cytotoxicity studied in vitro. The results provided initial insights into the complex relationship among the molecular structures, self-assembly, and cytotoxicity of the studied compounds.
SN - 2632-8682
ER -