Biological Activities of Symbioimines

Symbioimine (35) inhibited osteoclastogenesis of the murine monocytic cell line RAW264, which can differentiate into osteoclasts following treatment with receptor activator of nuclear factor-^B ligand (RANKL) (EC5o = 44 ^g/mL) [71]. RANKL induces the formation of osteoclast-like multinucleated cells in cultures of bone marrow cells [75]. Symbioimine (35) inhibited an increase in sRANKL-induced TRAP activity of preosteoclast cells. Meanwhile, it did not affect cell viability even at 100 ^g/mL. Thus, symbioimine is a potential antiresorptive drug for the prevention and treatment of osteoporosis in postmenopausal women.

Symbioimine (35) also significantly inhibited cyclooxygenase-2 (COX-2) activity (32%) at 10 ^M. Meanwhile, it had only weak inhibitory ability (5%) toward COX-1 at 10 ^M [72]. The overexpression of COX-2 has been observed in many kinds of tumors, and its role in carcinogenesis and angiogenesis has been extensively investigated [76,77]. Several COX-2-selective inhibitors, such as rofecoxib, celecoxib, and sulindac, have been developed. Because of its moderate subtype specificity, symbioimine (35) may be useful for the development of new nonsteroid anti-inflammatory drugs (NSAID) to treat COX-associated diseases, such as inflammatory diseases and cancer.

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