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Information × Registration Number 0225U000283, (0124U002507) , R & D reports Title Calixarene-methylene-bis-phosphonic acids as potential osteoprotective agents in the complex therapy of bone tissue diseases with vitamin D3. popup.stage_title Дослідження фізико-хімічних, антиоксидантних та цитотоксичних властивостей нових каліксарен-метилен-біс-фосфонових кислот in vitro. Head Labudzynskyi Dmytro O., Кандидат біологічних наук Registration Date 08-01-2025 Organization Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine popup.description1 Study of potential anti-resorptive and regulatory effects of unique calixarene-methylene-bis-phosphonic acids in vitro and in vivo both individually and in combination with vitamin D3. popup.description2 By combining methods of bioinformatics analysis and virtual screening from a wide range of potential options, several bisphosphonate analogs were selected and synthesized, with calixarene-4- and 6-arene scaffolds, and methylene-bis-phosphonic acid residues chosen as the radicals. To further investigate the biological, specifically anti-resorptive properties of the calixarene-methylene-bis-phosphonic acids, their effects on the metabolic activity of RAW264.7 cells were studied using the MTT assay; their overall antioxidant, anti-oxidative, and radical-neutralizing activities in vitro were examined; their impact on the generation of reactive oxygen species (ROS) in activated RAW264.7 cells was explored, as well as their ability to inhibit the enzymatic activity of farnesyl pyrophosphate synthase; and the ability of the compounds to induce apoptosis and regulate the expression of key target genes in murine macrophage cells (RAW264.7) was also studied. The obtained results regarding the pro-/antioxidant properties of the calixarene-methylene-bis-phosphonic acids and their inhibitory impact on elements of the mevalonate intracellular pathway, in comparison to zoledronic acid, were complemented by studies of their overall cytotoxicity and pro-apoptotic effects. Moreover, the combination of molecular-biochemical methods allowed for the investigation of the direct or indirect regulatory effects of these compounds on RAW264.7 cells at the level of transcription and mRNA expression of target genes. The results suggest that certain representatives of the studied calixarene-methylene-bis-phosphonic acids exhibit high inhibitory anti-resorptive efficacy with a lower level of cytotoxicity, which could be promising for the development of future drugs with fewer side effects than existing branded anti-resorptive agents.  Product Description popup.authors Bilous Vasil L. Siromolot Andrii A. popup.nrat_date 2025-01-08 Close