通过二苯乙烯酰胺衍生物诱导成骨细胞分化：潜在的成骨剂。
Induced osteoblast differentiation by amide derivatives of stilbene: The possible osteogenic agents.
机构信息
Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Kukrail Road, Lucknow 226015, India.
Division of Endocrinology, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow 226 031, India.
出版信息
Bioorg Med Chem Lett. 2020 Jun 1;30(11):127138. doi: 10.1016/j.bmcl.2020.127138. Epub 2020 Mar 25.
A series of amide derivatives of stilbene was synthesized and investigated for osteogenic activity. Out of sixteen, seven compounds viz19c, 19g, 19i, 24b, 25a, 25c and 26a showed significant osteoblast differentiation within 1 pM-1 µM concentrations. Amongst all, 26a was identified as most active molecule which presented effective mineralization of osteoblasts and expression of mRNA of osteogenic marker gene such as BMP-2, ALP, and Runx-2 at 1 pM. In estrogen-deficient balb/c mice, 26a showed significant osteogenic activity at 5 mg-kg body weight dose. The protein expression study for estrogen receptors α and β (ER-α & ER-β) using mouse calvarial osteoblasts (MCOs) and molecular docking analyses showed preferential expression of ER-β by 26a indicating the possibility of ER-β mediated osteogenic activity of 26a.
合成了一系列二苯乙烯的酰胺衍生物，并研究了它们的成骨活性。在这 16 个化合物中，有 7 个化合物（19c、19g、19i、24b、25a、25c 和 26a）在 1pM-1µM 浓度范围内表现出显著的成骨细胞分化。在所有化合物中，26a 被鉴定为最活跃的分子，它能有效促进成骨细胞的矿化，并表达成骨标志物基因（如 BMP-2、ALP 和 Runx-2）的 mRNA。在去势雌性 balb/c 小鼠中，26a 在 5mg-kg 体重剂量下表现出显著的成骨活性。使用小鼠颅骨成骨细胞（MCOs）进行雌激素受体 α 和 β（ER-α 和 ER-β）的蛋白表达研究以及分子对接分析表明，26a 优先表达 ER-β，表明 26a 可能通过 ER-β 介导成骨活性。
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