Inhibitory activity against bone resorption

Our studies on biologically active substances of this plant led to isolation of diterpenoids showing cytotoxicity [8], inhibitory effects on fi-glucuronidase [9], H+,K+-ATPase [10-12], replication of herpes simplex virus type 1 (HSV-1) [8,13,14] and bone resorption stimulated by parathyroid hormone (PTH) [15], and antitumor [16] and antitumor promoting effects [17]. In addition, some flavonoids possessing cytotoxicity [18], inhibitory activity against [3-glucuronidase [19] and antiviral activity [20] were also obtained from whole plants. 

Cathepsins comprise a family of enzymes within the papain superfamily of cysteine proteases that play important roles in physiological processes such as bone resorption, tumor metathesis, and rheumatoid arthritis. Recently we reported a series of novel compounds which exhibit potent inhibitory activity against cathepsin L. To explore further this novel class, we have constructed a library of thiocarbazates and tested them against a panel of serine and cysteine proteases. Preliminary studies reveal that some of these compounds are highly selective for cathepsin S over B and L, with nanomolar IC50 values. The results of these studies will be described. 

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