Semisynthesis and Cytotoxic Activities of Novel Oxime Ester Derivatives of the Diterpene Stemodin

Stemodin (1) is a diterpene produced by Stemodia maritima L. (Scrophulariaceae) and shows antiviral and tumor cell proliferation inhibitory activities. Chemical modifications of 1 were performed to produce the known stemodinone (2), two new stemodinone oximes, Z (3) and E (4), and seven new oxime esters derivatives (5, 6, 7, 8, 9, 10, and 11). All derivatives were evaluated for their cytotoxic activity in HL60 (promyelocytic leukemia), SNB-19 (astrocytoma), HCT-116 (colon carcinoma), and PC3 (prostate) human cancer cell lines, and L929 (healthy murine cells). Oximes 3 and 4 showed lower cytotoxic values than 1 against all cancer cell lines tested. However, esters 9 and 10 exhibited cell growth inhibition percentages higher than 1 against PC3, SNB-19, and HCT-116 cancer cell lines, ranging from 62.96 to 94.27%. Many of these values exceed that presented by doxorubicin (66.05-86.87%). All compounds showed no cytotoxic effect on healthy cells at the tested concentration of 25 µg mL-1.