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Information × Registration Number 0225U005353, (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 терапевтичного впливу каліксарен-метилен-біс-фосфонових кислот на стан кісткової тканини, систему гемостазу тарівень маркерів запалення у щурів із оваріоектомією in vivo. Head Labudzynskyi Dmytro O., Кандидат біологічних наук Registration Date 30-12-2025 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 Despite the high clinical efficacy of bisphosphonates, their use is limited by risk of adverse effects, which underscores the need to identify new antiresorptive compounds with a milder mechanism of action. Using bioinformatic analysis and virtual screening approaches, a series of calixarene–methylene-bisphosphonic acids were synthesized as structural analogues of bisphosphonates, followed by their stepwise biological evaluation. At the in vitro stage, several compounds, particularly C145 and C1249, demonstrated pronounced inhibitory activity against farnesyl pyrophosphate synthase, along with antioxidant and regulatory properties, and ability to modulate apoptosis and the expression of key osteoclastogenesis-related genes in RAW264.7 macrophage cells, in a manner comparable to the reference drug zoledronate. These findings provided the rationale for selecting the most promising compounds for subsequent in vivo evaluation.In a rat model of ovariectomy-induced osteoporosis, administration of calixarene–methylene-bisphosphonic acids, especially compound C145, resulted in partial normalization of bone resorption markers (DPD, CTX-1, TRAP, cathepsin K) and bone formation markers (P1NP, osteocalcin), as well as modulation of the Wnt/β-catenin signaling pathway at both protein expression and transcriptional levels. Computed tomography data and histomorphological analysis further confirmed a reduction in the severity of osteoporotic changes and stabilization of bone microarchitecture in treated animals compared with untreated ovariectomized controls.Taken together, these results indicate that calixarene–methylene-bisphosphonic acids, particularly compound C145, combine antiresorptive efficacy with a milder regulatory impact on bone metabolism compared with zoledronic acid. This provides experimental basis for further pharmacological studies and supports the consideration of compound C145 as a promising candidate for the development of next-generation antiresorptive agents. Product Description popup.authors Siromolot Andrii A. Vasyl L. Bilous popup.nrat_date 2025-12-30 Close