Studies On The Synthesis And Antitumor Activities Of Novel Benzofuran And Carbazole Derivatives

Malignant tumor is the second biggest killer except cardiovasscular disease, whichis a serious threat to human health. Therefore, the search and discovery of newanticancer drugs has been widely studied. In this thesis, based on the pharmacophoreswith antitumor activity in many natural products and drug molecules, lots of molecularhybrid compounds have been synthesized in order to find novel antitumor leadcompounds.This thesis is consisted of four chapters.In chapter one, research progress on the synthese and biological activities ofbenzofuran, dibenzofuran and carbazole derivatives were briefly reviewed.In chapter two, three seris of thirty-two benzofuran-triazole hybrid compounds andtheir trizolelium salts were synthesized and tested in vitro against a panel of fivedifferent human tumor cell lines. The results show that many compounds such as18、21、28、29、31、34、35and36exhibited potent antitumor activities. Especially,compounds29,30and36displayed selective activities against A-549, MCF-7andSW480. Compound31exhibited selective activities against HL-60and A549with IC50values of0.62and1.60μM.In chapter three, two series of twenty-four dibenzofuran-trizole hybrid compoundsand their trizolelium salts were synthesized and tested in vitro against a panel of fivedifferent human tumor cell lines. The results show that compounds28and29werefound to be the most potent derivatives with IC50values2.77~3.63μM against all ofhuman tumor cell lines, while compound19exhibited selective activity againstleukemia (HL-60) and breast carcinoma (MCF-7) cell lines with IC50values of0.80and1.76μM, respectively.In chapter four, five series of fifty-five dibenzofuran-trizole hybrid compounds andtheir trizolelium salts were synthesized. Compared with benzofuran-trizolelium salts,both trizolium and imidazolium salts displayed high activities. Especially, compound47was found to be the most potent derivative against cervical carcinoma (Hela) with IC50of0.019μM.To be brief, one hundred and eleven novel compounds were synthesized and tested invitro against a panel of human tumor cell lines. On this basis, the analysis ofstructure–activity relationships and diversity-oriented synthesis of such heterocyclic compound library will be further studies, which can lay a foundation for the discoveryof lead compounds with potent antitumor activity.