Calcium Chelidonate: Semi-Synthesis, Crystallography, and Osteoinductive Activity In Vitro and In Vivo
Calcium chelidonate [Ca(ChA)(H<sub>2</sub>O)<sub>3</sub>]<sub>n</sub> 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<sub>2&l...
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| Format: | Article |
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MDPI AG
2021-06-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/6/579 |
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| author | Elena Avdeeva Ekaterina Porokhova Igor Khlusov Tatyana Rybalova Elvira Shults Larisa Litvinova Valeria Shupletsova Olga Khaziakhmatova Irina Sukhodolo Mikhail Belousov |
| author_facet | Elena Avdeeva Ekaterina Porokhova Igor Khlusov Tatyana Rybalova Elvira Shults Larisa Litvinova Valeria Shupletsova Olga Khaziakhmatova Irina Sukhodolo Mikhail Belousov |
| author_sort | Elena Avdeeva |
| collection | DOAJ |
| description | Calcium chelidonate [Ca(ChA)(H<sub>2</sub>O)<sub>3</sub>]<sub>n</sub> 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<sub>2</sub>O)<sub>3</sub>]<sub>n</sub> 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. |
| first_indexed | 2024-03-10T10:20:08Z |
| format | Article |
| id | doaj.art-1197586d148a496ba593c2ce5e858230 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T10:20:08Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-1197586d148a496ba593c2ce5e8582302023-11-22T00:30:10ZengMDPI AGPharmaceuticals1424-82472021-06-0114657910.3390/ph14060579Calcium Chelidonate: Semi-Synthesis, Crystallography, and Osteoinductive Activity In Vitro and In VivoElena Avdeeva0Ekaterina Porokhova1Igor Khlusov2Tatyana Rybalova3Elvira Shults4Larisa Litvinova5Valeria Shupletsova6Olga Khaziakhmatova7Irina Sukhodolo8Mikhail Belousov9Department of Pharmaceutical Analysis, Siberian State Medical University, 634050 Tomsk, RussiaDepartment of Morphology and General Pathology, Siberian State Medical University, 634050 Tomsk, RussiaDepartment of Morphology and General Pathology, Siberian State Medical University, 634050 Tomsk, RussiaCenter of Spectral Investigations, Novosibirsk Institute of Organic Chemistry, Siberian Branch, 630090 Novosibirsk, RussiaLaboratory of Medicinal Chemistry, Novosibirsk Institute of Organic Chemistry, Siberian Branch, 630090 Novosibirsk, RussiaCenter for Immunology and Cell Biotechnology, Immanuel Kant Baltic Federal University, 236041 Kaliningrad, RussiaCenter for Immunology and Cell Biotechnology, Immanuel Kant Baltic Federal University, 236041 Kaliningrad, RussiaCenter for Immunology and Cell Biotechnology, Immanuel Kant Baltic Federal University, 236041 Kaliningrad, RussiaDepartment of Morphology and General Pathology, Siberian State Medical University, 634050 Tomsk, RussiaDepartment of Pharmaceutical Analysis, Siberian State Medical University, 634050 Tomsk, RussiaCalcium chelidonate [Ca(ChA)(H<sub>2</sub>O)<sub>3</sub>]<sub>n</sub> 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<sub>2</sub>O)<sub>3</sub>]<sub>n</sub> 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.https://www.mdpi.com/1424-8247/14/6/579calcium chelidonatesemi-synthesisX-ray diffraction analysisosteogenic activity |
| spellingShingle | Elena Avdeeva Ekaterina Porokhova Igor Khlusov Tatyana Rybalova Elvira Shults Larisa Litvinova Valeria Shupletsova Olga Khaziakhmatova Irina Sukhodolo Mikhail Belousov Calcium Chelidonate: Semi-Synthesis, Crystallography, and Osteoinductive Activity In Vitro and In Vivo Pharmaceuticals calcium chelidonate semi-synthesis X-ray diffraction analysis osteogenic activity |
| 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 | calcium chelidonate semi-synthesis X-ray diffraction analysis osteogenic activity |
| url | https://www.mdpi.com/1424-8247/14/6/579 |
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