Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, (CSIR-CDRI), BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, P.O. Box 173, Lucknow 226031, India.
Eur J Med Chem. 2013;70:802-10. doi: 10.1016/j.ejmech.2013.10.060. Epub 2013 Nov 1.
Anti-osteoporotic effects of the newly synthesized coumarin-pyridine hybrids were evaluated in primary cultures of rat calvarial osteoblasts in vitro. Compounds 6a, i, j and k were potent in stimulating osteoblast differentiation and mineralization as assessed by the alkaline phosphatase production and alizarin red-S staining assay, respectively. These compounds were also found to be nontoxic in osteoblast cells as compared to the control group in an MTT assay. Furthermore, the effect of these compounds on the transcript levels of osteogenic genes revealed that the compound 6j robustly enhanced mineralization of the osteogenic genes in calvarial osteoblasts. In this context, compound 6j was selected as a potential lead for further structural optimization in the development of new anti-osteoporotic agents.
新型香豆素-吡啶杂合体的抗骨质疏松作用在体外大鼠颅骨成骨细胞原代培养中进行了评价。通过碱性磷酸酶产生和茜素红 S 染色测定，分别评估化合物 6a、i、j 和 k 对成骨细胞分化和矿化的刺激作用。与对照组相比，这些化合物在 MTT 测定中在成骨细胞中也被发现是无毒的。此外，这些化合物对成骨基因转录水平的影响表明，化合物 6j 可显著增强颅骨成骨细胞中成骨基因的矿化。在这种情况下，化合物 6j 被选为进一步结构优化以开发新型抗骨质疏松药物的潜在先导化合物。
