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Calcium Chelidonate: Semi-Synthesis, Crystallography, and Osteoinductive Activity In Vitro and In Vivo

Calcium chelidonate [Ca(ChA)(H(2)O)(3)](n) was obtained by semi-synthesis using natural chelidonic acid. The structure of the molecular complex was determined by X-ray diffraction analysis. The asymmetric unit of [Ca(ChA)(H(2)O)(3)](n) includes chelidonic acid coordinated through three oxygen atoms,...

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Autores principales: Avdeeva, Elena, Porokhova, Ekaterina, Khlusov, Igor, Rybalova, Tatyana, Shults, Elvira, Litvinova, Larisa, Shupletsova, Valeria, Khaziakhmatova, Olga, Sukhodolo, Irina, Belousov, Mikhail
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235635/
https://www.ncbi.nlm.nih.gov/pubmed/34204329
http://dx.doi.org/10.3390/ph14060579
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author Avdeeva, Elena
Porokhova, Ekaterina
Khlusov, Igor
Rybalova, Tatyana
Shults, Elvira
Litvinova, Larisa
Shupletsova, Valeria
Khaziakhmatova, Olga
Sukhodolo, Irina
Belousov, Mikhail
author_facet Avdeeva, Elena
Porokhova, Ekaterina
Khlusov, Igor
Rybalova, Tatyana
Shults, Elvira
Litvinova, Larisa
Shupletsova, Valeria
Khaziakhmatova, Olga
Sukhodolo, Irina
Belousov, Mikhail
author_sort Avdeeva, Elena
collection PubMed
description Calcium chelidonate [Ca(ChA)(H(2)O)(3)](n) was obtained by semi-synthesis using natural chelidonic acid. The structure of the molecular complex was determined by X-ray diffraction analysis. The asymmetric unit of [Ca(ChA)(H(2)O)(3)](n) includes chelidonic acid coordinated through three oxygen atoms, and three water ligands. The oxygen atoms of acid and oxygen atoms of water from each asymmetric unit are also coordinated to the calcium of another one, forming an infinite linear complex. Calcium geometry is close to the trigonal dodecahedron (D2d). The intra-complex hydrogen bonds additionally stabilize the linear species, which are parallel to the axis. In turn the linear species are packed into the 3D structure through mutual intercomplex hydrogen bonds. The osteogenic activity of the semi-synthetic CaChA was studied in vitro on 21-day hAMMSC culture and in vivo in mice using ectopic (subcutaneous) implantation of CaP-coated Ti plates saturated in vitro with syngeneic bone marrow. The enhanced extracellular matrix ECM mineralization in vitro and ectopic bone tissue formation in situ occurred while a water solution of calcium chelidonate at a dose of 10 mg/kg was used. The test substance promotes human adipose-derived multipotent mesenchymal stromal/stem cells (hAMMSCs), as well as mouse MSCs to differentiate into osteoblasts in vitro and in vivo, respectively. Calcium chelidonate is non-toxic and can stimulate osteoinductive processes.
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spelling pubmed-82356352021-06-27 Calcium Chelidonate: Semi-Synthesis, Crystallography, and Osteoinductive Activity In Vitro and In Vivo Avdeeva, Elena Porokhova, Ekaterina Khlusov, Igor Rybalova, Tatyana Shults, Elvira Litvinova, Larisa Shupletsova, Valeria Khaziakhmatova, Olga Sukhodolo, Irina Belousov, Mikhail Pharmaceuticals (Basel) Article Calcium chelidonate [Ca(ChA)(H(2)O)(3)](n) was obtained by semi-synthesis using natural chelidonic acid. The structure of the molecular complex was determined by X-ray diffraction analysis. The asymmetric unit of [Ca(ChA)(H(2)O)(3)](n) includes chelidonic acid coordinated through three oxygen atoms, and three water ligands. The oxygen atoms of acid and oxygen atoms of water from each asymmetric unit are also coordinated to the calcium of another one, forming an infinite linear complex. Calcium geometry is close to the trigonal dodecahedron (D2d). The intra-complex hydrogen bonds additionally stabilize the linear species, which are parallel to the axis. In turn the linear species are packed into the 3D structure through mutual intercomplex hydrogen bonds. The osteogenic activity of the semi-synthetic CaChA was studied in vitro on 21-day hAMMSC culture and in vivo in mice using ectopic (subcutaneous) implantation of CaP-coated Ti plates saturated in vitro with syngeneic bone marrow. The enhanced extracellular matrix ECM mineralization in vitro and ectopic bone tissue formation in situ occurred while a water solution of calcium chelidonate at a dose of 10 mg/kg was used. The test substance promotes human adipose-derived multipotent mesenchymal stromal/stem cells (hAMMSCs), as well as mouse MSCs to differentiate into osteoblasts in vitro and in vivo, respectively. Calcium chelidonate is non-toxic and can stimulate osteoinductive processes. MDPI 2021-06-17 /pmc/articles/PMC8235635/ /pubmed/34204329 http://dx.doi.org/10.3390/ph14060579 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Avdeeva, Elena
Porokhova, Ekaterina
Khlusov, Igor
Rybalova, Tatyana
Shults, Elvira
Litvinova, Larisa
Shupletsova, Valeria
Khaziakhmatova, Olga
Sukhodolo, Irina
Belousov, Mikhail
Calcium Chelidonate: Semi-Synthesis, Crystallography, and Osteoinductive Activity In Vitro and In Vivo
title Calcium Chelidonate: Semi-Synthesis, Crystallography, and Osteoinductive Activity In Vitro and In Vivo
title_full Calcium Chelidonate: Semi-Synthesis, Crystallography, and Osteoinductive Activity In Vitro and In Vivo
title_fullStr Calcium Chelidonate: Semi-Synthesis, Crystallography, and Osteoinductive Activity In Vitro and In Vivo
title_full_unstemmed Calcium Chelidonate: Semi-Synthesis, Crystallography, and Osteoinductive Activity In Vitro and In Vivo
title_short Calcium Chelidonate: Semi-Synthesis, Crystallography, and Osteoinductive Activity In Vitro and In Vivo
title_sort calcium chelidonate: semi-synthesis, crystallography, and osteoinductive activity in vitro and in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235635/
https://www.ncbi.nlm.nih.gov/pubmed/34204329
http://dx.doi.org/10.3390/ph14060579
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