DNA嵌入剂和DNA拓扑异构酶Ⅱ抑制剂与抗癌作用的关系——介绍两种抗癌药物的筛选方法

THE RELATIONSHIP OF DNA INTERCALATE AGENTS AND INHIBITORS OF DNA TOPOISOMERASE II AND ANT 1TUMOR ACTION-INTRODUCING TWO METHODS FOR ANTITUMOR DRUG SCREENING

本文介绍两种抗癌药物的筛选方法。实验表明,对pBR322 DNA能起嵌入和断裂作用或对DNA拓扑异构酶Ⅱ有抑制作用的化合物可能具有抗癌作用。吖啶衍生物9-(2-4-二氯苯氧乙酰氨基)吖啶,9-(2-4-5-三氯苯氧乙酰氨基)吖啶和9-(对-氯苯氧乙酰氨基)吖啶对pBR322 DNA能起嵌入和断裂作用。它们对体外生长细胞显示强力的细胞毒作用。山茶A和山茶C化合物对拓扑异构酶Ⅱ有强力的抑制作用,对体外培养细胞亦具有细胞毒作用。

Two methods for antitumor drug screening are introduced in this paper. Experiments showed that the drugs which are able to intercalate into the supercoiled pBR322 DNA and induce DNA chain cleavage or inhibit the activity of DNA topoisomerase Ⅱ would have antitumor effect. Acridine derivatives, 9-(2-4-dichloro-phenoxyacetyl-amino) -acridine, 9-(2-4-5-trichlorophenoxyacetyl-amino)-acridine and 9-(p-chloro-phenoxyacetyl-amino) -acridine, can intercalate into the supercoiled pBR322 DNA and have DNA cleaving effect. They showed marked cytotoxic effect on nasopharyngeal carcinoma cell line (CEN2) in vitro. Tea extracts, compound A and C, can dramatically inhibit the activity of DNA topoisomerase Ⅱ and have cytotoxic effect on cultured Hela cells in vitro.