Jin G Z, Song G Y, Zheng X G, Kim Y, Sok D E, Ahn B Z
College of Pharmacy, Chungnam National University, Taejon, Korea.
Arch Pharm Res. 1998 Apr;21(2):198-206. doi: 10.1007/BF02974028.
Fourty eight derivatives of 2-(1-oxyalkyl)-1,4-dioxy-9,10-anthraquinone were synthesized, and their antitumor activity was evaluated. On the whole, 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinones (DHAQ = 1,4-dihydroxy-9,10-anthraquinone) showed stronger cytotoxic activity against L1210 cells than 2-(1-hydroxyalkyl)-1,4-dimethoxy-9,10-anthraquinones(DMAQ = 1,4-dimethoxy-9,10-anthraquinone), implying that free hydroxy groups at C-1 and C-4 of the anthraquinone structure are necessary for the cytotoxic activity. The bioactivity of 2-(1-hydroxyalkyl)-DHAQ derivatives differed according to the size of alkyl group at C-1; while the elongation of alkyl group over 7 carbon atoms failed to enhance the bioactivity, the derivatives possessing alkyl moiety of 1-6 carbon atoms showed an increase in the cytotoxicity and the antitumor activity in Sarcoma-180; 2-hydroxymethyl-DHAQ (ED50, 15 micrograms/ml; T/C, 125%), 2-(1-hydroxyethyl)-DHAQ(1.9 micrograms/ml; 139.2%), 2-(1-hydroxypropyl)-DHAQ (7.2 micrograms/ml; 135.1%), 2-(1-hydroxybutyl)-DHAQ (10.2 micrograms/ml; 125.3%), 2-(1-hydroxypentyl)-DHAQ (23.7 micrograms/ml; 110.1%), and 2-(1-hydroxyhexyl)-DHAQ (58 micrograms/ml; 108%). Next, 2-(1-Hydroxyalkyl)-DHAQ derivatives were acetylated to produce 2-(1-acetoxyalkyl)-DHAQ analogues. Although the acetylation somewhat enhanced the cytotoxicity, but not the antitumor action. In addition, the presence of phenyl group at C-1' enhanced the cytotoxicity and the T/C value, compared to alkyl groups of same size; 2-(1-hydroxy-1-phenyl)-DHAQ (ED50, 5.6 micrograms/ml; T/C, 137%).
合成了48种2-(1-氧代烷基)-1,4-二氧基-9,10-蒽醌衍生物，并对其抗肿瘤活性进行了评估。总体而言，2-(1-羟烷基)-1,4-二羟基-9,10-蒽醌（DHAQ = 1,4-二羟基-9,10-蒽醌）对L1210细胞的细胞毒性活性比2-(1-羟烷基)-1,4-二甲氧基-9,10-蒽醌（DMAQ = 1,4-二甲氧基-9,10-蒽醌）更强，这意味着蒽醌结构中C-1和C-4位的游离羟基对于细胞毒性活性是必需的。2-(1-羟烷基)-DHAQ衍生物的生物活性根据C-1位烷基的大小而有所不同；虽然烷基超过7个碳原子的延长未能增强生物活性，但具有1-6个碳原子烷基部分的衍生物在肉瘤-180中显示出细胞毒性和抗肿瘤活性的增加；2-羟甲基-DHAQ（ED50，15微克/毫升；T/C，125%）、2-(1-羟乙基)-DHAQ（1.9微克/毫升；139.2%）、2-(1-羟丙基)-DHAQ（7.2微克/毫升；135.1%）、2-(1-羟丁基)-DHAQ（10.2微克/毫升；125.3%）、2-(1-羟戊基)-DHAQ（23.7微克/毫升；110.1%）和2-(1-羟己基)-DHAQ（58微克/毫升；108%）。接下来，将2-(1-羟烷基)-DHAQ衍生物乙酰化以制备2-(1-乙酰氧基烷基)-DHAQ类似物。虽然乙酰化在一定程度上增强了细胞毒性，但没有增强抗肿瘤作用。此外，与相同大小的烷基相比，C-1'位存在苯基增强了细胞毒性和T/C值；2-(1-羟基-1-苯基)-DHAQ（ED50，5.6微克/毫升；T/C，137%）。
