Osteoporosis is one of the most common diseases for aged people, posing a heavy burden to our aging society. Inhibition of osteoclastogenesis is a main strategy to prevent bone loss or bone micro architecture deterioration caused by postmenopausal osteoporosis. In current study, a series of quinoxalinefused oleanolic acid (QOA) derivatives were designed and synthesized. Their inhibitory activity on receptor activator of nuclear factor-kB ligand (RANKL)-induced osteoclastogenesis was evaluated using a cell-based tartrate-resistant acid phosphatase (TRAP) assay. The most potent compound, QOA derivative 5 l, showed an IC 50 at 62.4 nM, and cytotoxicity assay of bone marrow-derived monocyte/macrophage (BMDMs) suggested that the inhibition of 5 l on osteoclast differentiation was not due to its cytotoxicity. More importantly, 5 l attenuated bone loss in the bilateral ovariectomy (OVX) mice model, and preliminary mechanism study indicated that 5 l affected the early stage of osteoclastogenesis. Our data demonstrated that these QOA derivatives might serve as potential leads for the development of new anti-osteoporosis agents.
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