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        Biological evaluations of novel 2,3,3-Trisphosphonate in osteoclastic and osteoblastic activities

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        GMO_1_121.pdf (PDF, 4Mb)
        Author
        Cheong, Yuen Ki
        Huang, Mei
        Detsch, Rainer
        Boccaccini, Aldo R.
        Ren, Guogang
        Attention
        2299/20649
        Abstract
        Bisphosphonates (BPs) are the first line treatment for many bone diseases including hypercalcimia associated with bone malignancies. In this paper, we introduce a new analogue of bisphosphonate called the 2,3,3-Trisphosphonate (2,3,3-TriPP) that was synthesised in a two steps reaction. In vitro investigations using a medically known bisphosphonate (Etidronate) and the 2,3,3-TrisPP were performed with an aim to evaluate biological effect of this novel compound in major bone cells. 2,3,3-TrisPP showed to have potential to supress the bone resorption process, as our data found that this novel compound exhibited cytotoxic effect in osteoclastic cells at a low concentration of 0.172 mg/mL (LC50). A molecular docking computational simulation calculated a high level of binding affinity between the human farnesyl pyrophosphate synthase (hFPPS) and 2,3,3-TrisPP. This calculation suggested 2,3,3TrisPP may have undergone the mevalonate pathway to prevent the prenylation step during biosynthesis and subsequently resulted in the deactivation of osteoclastic cells. Finally, high levels of osteoblast mineralisation potentials were recorded upon treatments with 2,3,3-TrisPP (0.01-0.1 mg/ml), which implied 2,3,3-TrsiPP may also facilitate bone regeneration.
        Publication date
        2017-12-08
        Published in
        General Medicine Open
        Published version
        https://doi.org/10.15761/GMO.1000121
        Other links
        http://hdl.handle.net/2299/20649
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