Work

Probing the Hydrophobic Part of Analogues of the Incadronate-Evidence of Their Interaction with Immunological System of Sheep

Year: 2026

Type: article

Abstract: Background: Thirty-five analogues of a promising antiosteoporotic drug, incadronate, have been synthesized and evaluated for their antiproliferative activity against mouse macrophage-like J774E cells. These cells originated from identical precursors as osteoclasts and served to select the most active compounds. Two of them, n-heptyl- and n-octyl-aminomethylenebispohosphonic acids, were then used for the medication of sheep with induced osteoporosis. They demonstrated mild antiosteoporotic activity that was documented using bone histopathology. Additionally, a decrease in the immunological response to Corynebacterium pseudotuberculosis was observed as a major side effect accompanied by this medication. Methods: Aminomethylenebisphosphonates may be obtained in the three-component reaction of aliphatic amine, triethyl orthoformate and diethyl phosphite with the further acid hydrolysis of crude esters. The obtained N-substituted alkiloaminomethylenebisphosphonic acids are presented alongside with their in vitro activity toward mouse macrophages J774E. Results: The new families of aminomethylenebisphosphonic compounds synthesized by our approach may be of practical importance due to the significant cytotoxic activity in the cell cultures investigated. Two of them were chosen for further evaluation in the treatment of induced osteoporosis in sheep. Conclusions: In vivo studies confirmed the mild therapeutic effects of compounds 4 (N-(n-heptylamino)methylenebisphosphonic acid and 5 (N-(n-octylamino)methylenebisphosphonic acid; however, they are not suitable analogues of incadronate for consideration as potential drugs.

Source: Pharmaceuticals

DOI: 10.3390/ph19020256

Authors: Ewa Chmielewska, Joanna Wietrzyk, Jan Kuryszko, Zdzisław Kiełbowicz, Paweł Kafarski

Institutions: Wrocław University of Science and Technology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław University of Environmental and Life Sciences, University of Warmia and Mazury in Olsztyn

Language: English

Topic: Bone health and treatments

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499