Formononetin Derivative for Osteoporosis by Simultaneous Regulating Osteoblast and Osteoclast.

Seven new formononetin derivatives (-) were designed and prepared from formononetin (phase II phytoestrogen). The derivatives 9-butyl-3-(4-methoxyphenyl)-9,10-dihydro-4,8-chromeno[8,7-][1,3]oxazin-4-one () and 9-(furan-3-ylmethyl)-3-(4-methoxyphenyl)-9,10-dihydro-4,8-chromeno[8,7-][1,3]oxazin-4-one () promoted significant osteoblast formation by modulating the BMP/Smad pathway. Compound exhibited potent antiosteoclastogenesis activity in RANKL-induced RAW264.7 cells and ovariectomy (OVX)-induced osteoporosis in mice by regulation of the RANK/RANKL/OPG pathway. Compound regulated osteoblast and osteoclast simultaneously and showed better effect than the well-known drug ipriflavone , suggesting as a patented antiosteoporosis candidate.