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Information × Registration Number 0223U001893, 0121U112008 , R & D reports Title Study of biological properties of new pyrazole-containing bisphosphonates as potential regulators of bone metabolism popup.stage_title Head Labudzynskyi Dmytro O., Кандидат біологічних наук Registration Date 04-02-2023 Organization Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine popup.description2 Loss of bone mass is the main cause of most diseasesskeleton Calcium, estrogen, calcitonin, bisphosphonates, and vitamin D3 preparations are considered to be agents capable of inhibiting bone loss by inhibiting bone tissue resorption. However, bisphosphonates are the first line of defense against bone loss. They remain one of the most effective means of treating diseases of the musculoskeletal system, and the development of new, more advanced analogues of them has wide prospects for practical application. By combining the methods of bioinformatics analysis and virtual screening, a number of bisphosphonate analogues were selected and synthesized from a wide range of possible options, and pyrazole derivatives were chosen as the radical. In order to further investigate the biological, in particular antiresorptive, properties of pyrazole-containing bisphosphonates, their influence on the metabolic activity of cells of the J774A.1 line and the primary culture of rat hepatocytes was investigated by the MTT method; their general antioxidant, antioxidant and DPPH-radical scavenging activity in vitro was studied; their effect on the synthesis of isoprenoids and cholesterol of the mevalonate pathway in J774A.1 cells, as well as their ability to inhibit the enzymatic activity of farnesyl pyrophosphate synthase was investigated. The obtained results of the study of both the pro-/antioxidant properties of pyrazole-containing bisphosphonates and their inhibitory effect on the elements of the mevalonate intracellular pathway allow qualitatively, in comparison with zoledronic acid, to be complemented by the study of their general level of cytotoxicity and proapoptotic action. The above-mentioned work results indicate that individual representatives of the studied bisphosphonates have a very high efficiency of inhibitory anti-resorptive action with a lower level of cytotoxicity.   Product Description popup.authors Paliienko Konstantin O. popup.nrat_date 2023-02-04 Close