Synthesis and evaluation of new coumarin-pyridine hybrids with promising anti-osteoporotic activities*

Abstract

Anti-osteoporotic effects of the newly synthesized coumarin-pyridine hybrids were evaluated in primary cultures of rat calvarial osteoblasts in vitro. Compounds 6a, 6i, 6j and 6k 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 non toxic 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 (Runx-2, BMP-2 and CoL-1) 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.