嘌呤磺胺衍生物的合成及抗肿瘤活性

合成了一系列结构全新的嘌呤磺胺类衍生物, 并应用溴化噻唑蓝四氮唑(MTT)法进行了初步体外抗肿瘤细胞增殖活性研究. 结果表明, 嘌呤环C2位、 N6位和N9位的取代对活性均有较大影响, C2位引入苯磺酰基哌嗪片段后有利于提高抗肿瘤活性. 化合物17d对3株肿瘤细胞PC-3, HCT116和K562 的增殖均有明显抑制作用, 且强度与阳性对照药Roscovitine相近.

Syntheses and Antitumor Activities of Purine-sulfonamides Derivatives†

As a new type of purine derivative, Roscovitine exhibits good antiproliferative activities to different types of tumor cell lines and currently has been investigated in Phase Ⅱ clinical trial. Previous structure-acti-vity relationship studies on Roscovitine suggested that the modification on C2, C6 and N9 positions of purine could significantly influence the antitumor acitivities. In this work, a biologically active fragment benzenesulfonamide was introduced to purine C2 position and totally 25 new purine-sulfonamides derivatives were synthesized and evaluated antiproliferative activities in some tumor cell lines by MTT assay. The results show that the substitutions on C2, N6 and N9 positions of purine have a great impact on antitumor activity. And introducing phenylsulfonyl piperazine on C2 position of purine could obviously enhance antiproliferative activities. Among them, compound 17d shows similar inhibitory activities against PC-3, HCT116 and K562 tumor cell lines compared with Roscovitine.