倍半萜内酯（SL）第二十四部分。关于倍半萜内酯对人癌细胞组织培养细胞毒性活性的进一步研究。

Sesquiterpene lactones (SL) part XXIV. Further studies on cytotoxic activities of SL in tissue culture of human cancer cells.

作者信息

Hładoń B, Drozdz B, Holub M, Szafarek P, Klimaszewska O

出版信息

Pol J Pharmacol Pharm. 1978 Sep-Oct;30(5):611-20.

Abstract

Cytotoxicity of most of the 18 new sesquiterpene lactones (SL), derivatives of germacran, guaian, pseudoguaian, and selinan, and related glycosides was studied by tissue culture method on human KB and HeLa cell lines. Eleven compounds with ED50, activity values between 0.24 and 2.40 microgram/ml (9,2.10(-7)--9.1.10(-6) M) were qualified for further in vivo investigation. It seems that: a) unsaturated alpha-exo-methylene-gamma-lactone ring:-O-CO-C=CH2 conjugated with basic terpene carbocyclic skeleton plays the main role for cytotoxicity of SL. The next determinants of the activity are apparently: b) sesquiterpenoid carbocyclic grouping (germacranolides (GE), pseudoguaianolides (PGU), guaianolides (GU), c) the position of cyclization of gamma-lactone ring (C6--C12) or C8--C12), d) some substituents with an epoxide and/or keto-function in different positions of sesquiterpenoids. The natural and modified alpha-exo-methylene-guaianolide-C3-glycosides (GUG) are not significantly more potent than the remaining alpha-exo-methylene-gamma-lactones.

摘要

采用组织培养法，对18种新的倍半萜内酯（SL）及其衍生物（吉马烷、愈创木烷、伪愈创木烷和芹子烷的衍生物）以及相关糖苷对人KB和HeLa细胞系的细胞毒性进行了研究。11种化合物的半数有效剂量（ED50）活性值在0.24至2.40微克/毫升之间（9.2×10⁻⁷ - 9.1×10⁻⁶ M），有资格进行进一步的体内研究。似乎：a）与基本萜类碳环骨架共轭的不饱和α-外亚甲基-γ-内酯环-O-CO-C=CH₂对SL的细胞毒性起主要作用。活性的下一个决定因素显然是：b）倍半萜类碳环基团（吉马烷型内酯（GE）、伪愈创木烷型内酯（PGU）、愈创木烷型内酯（GU）），c）γ-内酯环的环化位置（C6 - C12）或C8 - C12），d）倍半萜类不同位置带有环氧化物和/或酮官能团的一些取代基。天然和修饰的α-外亚甲基愈创木烷型内酯-C3-糖苷（GUG）的效力并不比其余的α-外亚甲基-γ-内酯显著更高。