Design, Synthesis and Biological Evaluation of Novel Furanocoumarin Derivatives: Validation of Anti-Osteoporotic Efficacy In Vitro and In Vivo

<b>Background/Objectives</b>: Osteoporosis is a metabolic bone disease characterized by reduced bone mass and impaired bone microarchitecture. It has become a major clinical challenge due to the limitations of current therapeutic approaches. Isoimperatorin (ISO), a naturally occurring and biologically active furanocoumarin extracted from various traditional herbals, exhibits therapeutic potential in combating osteoporosis. However, toxicity limits its application. <b>Methods</b>: In vivo, compound <b>B15</b> was evaluated in an Ovariectomy (OVX) mice model, where treatment was associated with changes in bone microarchitecture parameters, modulation of serum bone metabolism markers, and alterations in the histopathological features of bone tissue. <b>Results</b>: In this study, a new series of furanocoumarin derivatives was designed and synthesized for the treatment of osteoporosis. Compared with ISO, compound <b>B15</b> has less toxicity and better ability to inhibit osteoclast formation in vitro. Compound <b>B15</b> could decelerate the progression of osteoporosis in ovariectomized mice. It is worth mentioning that the expression of estradiol in the serum of mice with excised ovaries was significantly increased by compound <b>B15</b>. <b>Conclusions</b>: These results imply that the novel furanocoumarin derivative <b>B15</b> is a promising therapeutic option for osteoporosis.