Synthesis of substituted triazolyl curcumin mimics that inhibit RANKL-induced osteoclastogenesis

Some promising new antiresorptive agents of potential utility for treating osteoporosis were uncovered in a curcumin mimics library possessing a substituted triazole moiety, which is synthesized by the Cu(I)-catalyzed Huisgen 1,3-cycloaddition reaction between two azido intermediates (9 and 10) and various alkynes (a–k). A tartarate-resistant acid phosphatase (TRAP) activity assay was carried out with RANKL-induced osteoclastogenesis of mouse monocyte/macrophage RAW264.7 cells; the results indicated that the curcumin mimics derived from intermediate 10 exhibited stronger inhibitory activity than 9. In particular, curcumin mimics 12h, 13c, and 13e strongly inhibited osteoclast differentiation.

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