2408
J. Y. Kim et al. / Bioorg. Med. Chem. Lett. 11 (2001) 2405–2408
Converting the ketone functionality to the correspond-
ing oximes (5 and 6) also appears to result in the loss of
cytotoxicity, probably due to the same reason described
above. These results suggest that the cytotoxicity profile
of betulinic acid dervatives may be sensitive to the size
of the substituents at the C-20 position in addition to
the electrostatic sensitivity. The hydroxyl amine 9,
methoxyl amine 10, primary alcohol 11, and the meth-
oxyl ether 12 also showed the loss of cytotoxity. Dihy-
drobetulinic acid (14) retained the cytotoxicity of the
parent compound, betulinic acid (1). Based on these
results, we conclude that C-20 position of betulinic acid is
not a favorable place to derivatize to improve cytotoxicity.
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1
5,16
observed (Table 1). In the previous studies,
human
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8
melanoma cell line MEL-2 (obtained from UIC medical
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1
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models, while human melanoma cell lines M14-MEL,
SK-MEL-2, and UACC-257 were used as the melanoma
models to evaluate the selective cytotoxicity. Interest-
ingly, the evaluation of these compounds using the dif-
ferent tumor cell lines did not show any selective
cytotoxicity. The results from both MTT reduction
assay and SRB staining assay were comparable that no
remarkable differences in cytotoxicity profile of the
compounds were noticed. Because of these unexpected
results, we are currently in a process of testing selected
betulinic acid derivatives, including the parent com-
pound, using other non-melanoma cell lines to evaluate
whether betulinic acid indeed possess selective cytotoxicity
against human melanoma cells or not.
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