嘌呤磺胺衍生物的合成及抗肿瘤活性

摘要

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。%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 benzenesul-fonamide was introduced to purine C2 position and totally 25 new purine-sulfonamides derivatives were synthe-sized 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 com-pared with Roscovitine.