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The systems of intermolecular interactions, including hydrogen bonds, in the crystal structures of the cocrystal of L -ascorbic (L -Asc) and nicotinic (Nic) acids and individual coformers are considered, and the hemolytic and cytotoxic activities of these compounds are studied in vitro. The influence of conformational differences of L -Asc molecules (total effective charge) on the formation of a network of H-bonds in the supramolecular structure of pristine L -Asc is revealed. Calculation of regioselectivity descriptors shows that the conformer of the L -Asc molecule in the L -AscNic cocrystal has higher activity compared to conformer molecules of the pristine L -Asc. No hemolysis caused by the solutions of tested acids and L -AscNic is shown. Selective cytotoxicity (antimetabolic effect according to the MTT test) of solutions of L -AscNic cocrystals against a 72-hour culture of MCF-7 breast cancer cell line versus healthy cells (mesenchymal stem cells and embryonic fibroblasts) is revealed. The possible relationship between the initial conformational state of the L -Asc molecules in the composition/structure of the studied solid compounds and the biological activity of solutions of these compounds requires further studies. [ABSTRACT FROM AUTHOR]

Chelidonic acid (ChA) is small molecule capable of inducing the differentiation of mesenchymal stem cells (MSCs) into osteoblasts and the formation of mineralized bone matrix (MBM) both in vitro and in vivo. However, the molecular mechanisms underlying these effects are unknown. Therefore, in silico modelling of potential molecular targets of ChA was performed. ChA was isolated from Saussurea controversa. The ability of ChA to induce in vitro differentiation MSCs into osteoblasts synthesizing MBM was detected using alizarin red staining. ChA osteogenic activity was studied in mice by in situ test of ectopic osteogenesis, using the subcutaneous implantation of syngeneic bone marrow on the calcium phosphate coated titanium plates. DIGEP-Pred web service was used to simulate in silico the effect of ChA on gene expression, and overrepresentation analysis to search for common ontologies and pathways. ChA linearly increased the number of single (R 2  = 0.92, p = 0.039) and the total areas of MBM sites (R 2  = 0.96, p = 0.019) in a 21-day MSC culture. Oral administration of ChA led to two to three times improved bone and bone marrow formation in situ. In silico modelling identified 306 genes (including 7 calcium import genes) and 9 signalling pathways potentially involved in ChA osteogenic effect and calcium metabolism in MSCs. In silico analysis revealed a list of key signalling pathways and genes for calcium influx into MSCs and their differentiation into osteoblasts as the first target candidates for studying real gene expression and molecular mechanisms of the ChA osteogenic effects., Competing Interests: Declarations. Conflict of interest: The authors declare no conflicts of interest. Ethical approval and consent to participate: Informed consent from the volunteers was obtained for the procedure, and the study was approved by the Local Ethics Committee of the Innovation Park of the Immanuel Kant Baltic Federal University (Permission Number 1 on February 28, 2019). The Local Ethics Committee of the Siberian State Medical University (approval number 6901 on 29 October 2018) approved the experimental study on animals. Consent for publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)