할로아세틸시코닌 유도체의 합성 및 항암성 평가

• 영문명: Haloacetylshikonin Derivatives: Synthesis and Evaluation of Antitumor Activity
• 발행기관: 대한약학회
• 저자명: 정상국(Xiang Guo Zheng) 김광주(Guang Zhu Jin) 송규용(Gyu Yong Song) 조훈(Hoon Cho) 안병준(Byung Zun Ahn)
• 간행물 정보: 『약학회지』제42권 제2호 (1998년), 159~164쪽, 전체 6쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 1998.04.30

영문 초록

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 (ED50, 0.142mcg/ml) > monobromoacetylshikonin (ED50. 0.158mcg/ml) > monoiodoacetylshikonin (ED50, 0.173mcg/ml). 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 (0.032mcg/ml) > dichloroacetylshikonin (0.059mcg/ml) > monochloroacetylshikonin (ED50, 0.142mcg/ml). Thus, the electron withdrawing effect seems to be important for the cytotoxicity of chloroacetylshikonin derivatives. Consistent with the above, dichloroacetylshikonin (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 cytoxic activities against L1210 cells exhibited lower T/C values. It seems that there is a relationship between the cytoxicity of haloacetylshikonin and their antitumor activity.

키워드

Haloacetylshikonin synthesis cytotoxicity L1210 and S-180 cells electronic and steric effect.