Formononetin Derivative for Osteoporosis by Simultaneous Regulating Osteoblast and Osteoclast

Seven new formononetin derivatives (1–7) were designed and prepared from formononetin (phase II
phytoestrogen). The derivatives 9-butyl-3-(4-methoxyphenyl)-9,10-dihydro-4H,8H-chromeno[8,7-e][1,3]oxazin-4-one
(2) and 9-(furan-3-ylmethyl)-3-(4-methoxyphenyl)-9,10-dihydro-4H,8H-chromeno[8,7-e][1,3]oxazin-4-one
(7) promoted significant osteoblast formation by modulating
the BMP/Smad pathway. Compound 7 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 7 regulated osteoblast and osteoclast simultaneously and showed better
effect than the well-known drug ipriflavone in vivo, suggesting 7 as a patented antiosteoporosis candidate.