할로아세틸시코닌 유도체의 합성 및 항암성 평가 : Synthesis and Evaluation of Antitumor Activity = Haloacetylshikonin Derivatives

다국어 초록 (Multilingual Abstract)

The secondary hydroxy group at side chain of shikonin structure was selectively acylated with various haloacetic acids in presence of dicyclohexylcarbodiimide and 4-dimethylaminopyridine to produce haloacetylshikonin derivatives. The cytotoxicity of monohaloacetylshikonin derivatives against L1210 cells increased in the following order: monochloroacetylshikonin (ED_50, 0.142 ㎍/㎖) nonobromoacetylshikonin (ED_50, 0.158㎍/㎖)>monoiodoacetylshikonin (ED_50, 0.173 ㎍/㎖). Introduction of larger halogen atoms decreased the cytotoxic activity, presumably due to steric hinderance. The cytotoxicity of chloroacetylshikonin derivatives was dependent on the number of chlorine atom, thus increasing in the following order : trichloroacetylshikonin (0.032 ㎍/㎖)>dichloroacetylshikonin (0.059 ㎍/㎖)> monochloroacetylshikonin (ED_50, 0.142 ㎍/㎖). Thus, the electron-withdrawing effect seems to be important for the cytotoxicity of chloracetylshikonin derivatives. Consistent with the above, dichloracetylshikonin (T/C, 182%) and trifluoroacetylshikonin (195%) showed higher T/C values than monochloroacetyl-(T/C, 122%), monobromoacetyl-(T/C, 154%) and monoiodoacetylshikonin (T/C, 117%) derivatives. Haloacetylshikonin derivatives showing lower cytotoxic activities against L1210 cells exhibited lower T/C values. It seems that there is a relationship between the cytotoxicity of haloacetylshikonin and their antitumor activity.