Synthesis of a Series of Heterocyclic N-Substituted Derivatives of Alendronic Acid and Their Preliminary Biological Evaluation.
- 1Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
- 2Department of Organic and Medicinal Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wrocław, Poland.
Abstract
The aim of this work was to examine the influence of introduction of heteroaromatic motifs like pyridyl and imidazole rings into alendronic acid molecule on its biological properties. For this purpose, a series of heterocyclic N-substituted alendronate derivatives were synthesized via a two-step, one-pot procedure. This procedure involves the condensation of alendronate and heteroaromatic aldehydes in the presence of triethylamine, which leads to the formation of appropriate Schiff bases, followed by the in situ reduction of the resulting imines with sodium borohydride. The study investigated the ability of the obtained bisphosphonates to bind to hydroxyapatite (HAP), as well as their antiproliferative effect against RAW 264.7 mouse macrophages, MCF-7 human breast cancer and MCF-10A normal breast epithelial cells. Among the tested derivatives, the 2-imidazole derivative (4f) and its N-methylated analog (4g) showed the best activity against both RAW 264.7 macrophages and MCF-7 cells, with an IC₅₀ value of 19.4 and 76.1 µM and of 26.4 and 107.9 µM, respectively. Furthermore, all synthesized derivatives were non-cytotoxic toward MCF-10A normal cells under the tested experimental conditions. The 4(5)-imidazole (4e) derivative showed the highest affinity to HAP.
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BibTeX
@article{nasulewiczgoldeman2026synthesis,
title = {{Synthesis of a Series of Heterocyclic N-Substituted Derivatives of Alendronic Acid and Their Preliminary Biological Evaluation.}},
author = {Anna Nasulewicz-Goldeman and Tomasz M Goszczyński and Joanna Wietrzyk and Waldemar Goldeman},
journal = {Chemistry \& biodiversity},
year = {2026},
month = oct,
doi = {10.1002/cbdv.71865},
url = {https://europepmc.org/article/MED/42908356},
note = {CC BY},
}
RIS
TY - JOUR
TI - Synthesis of a Series of Heterocyclic N-Substituted Derivatives of Alendronic Acid and Their Preliminary Biological Evaluation.
AU - Anna Nasulewicz-Goldeman
AU - Tomasz M Goszczyński
AU - Joanna Wietrzyk
AU - Waldemar Goldeman
PY - 2026
DA - 2026/10/01
JO - Chemistry & biodiversity
DO - 10.1002/cbdv.71865
UR - https://europepmc.org/article/MED/42908356
AB - The aim of this work was to examine the influence of introduction of heteroaromatic motifs like pyridyl and imidazole rings into alendronic acid molecule on its biological properties. For this purpose, a series of heterocyclic N-substituted alendronate derivatives were synthesized via a two-step, one-pot procedure. This procedure involves the condensation of alendronate and heteroaromatic aldehydes in the presence of triethylamine, which leads to the formation of appropriate Schiff bases, followed by the in situ reduction of the resulting imines with sodium borohydride. The study investigated the ability of the obtained bisphosphonates to bind to hydroxyapatite (HAP), as well as their antiproliferative effect against RAW 264.7 mouse macrophages, MCF-7 human breast cancer and MCF-10A normal breast epithelial cells. Among the tested derivatives, the 2-imidazole derivative (4f) and its N-methylated analog (4g) showed the best activity against both RAW 264.7 macrophages and MCF-7 cells, with an IC₅₀ value of 19.4 and 76.1 µM and of 26.4 and 107.9 µM, respectively. Furthermore, all synthesized derivatives were non-cytotoxic toward MCF-10A normal cells under the tested experimental conditions. The 4(5)-imidazole (4e) derivative showed the highest affinity to HAP.
SN - 1612-1872
SN - 1612-1880
ER -