Design, Synthesis And Antitumor Activity Of Benzofuran - Imidazole Compounds

According to a report released earlier, there are about 14.1 million new cancer cases and 8.2 million people die of cancer each year. About 57% cancer cases and 67% deaths are from developing country. Therefore, finding anti-cancer drugs have become a hot spot of drug research. During the previous research, chemists found out that some natural products containing benzofuran or imidazole unit have good antitumor activities. A series of benzofuran-imidazole hybrid molecules using molecular hybridization were designed and synthesized in this thesis, and were evaluated in vitro against a panel of human tumor cell lines. We found that some compounds showed good anti-tumor activities and high degree of selectivity. These compounds are likely to become a lead compound of anti-cancer drugs.This thesis includes two parts. In chapter 1, some traditional synthesis methods of benzofuran derivatives and the bioactivities of benzofuran derivatives and imidazole derivatives were reviewed.In chapter 2,41 novel hybrid compounds of benzofuran-imidazolium salts and 8 precursor compounds were designed and synthesis. These compounds were evaluated in vitro against five different human tumor cell lines. The results suggest that most of the testing samples expressed a good cytotoxicity by MTT assay. Compared with cisplatin (DDP), compound 24 was found to be the most potent derivative against breast carcinoma (MCF-7) and colon carcinoma (SW480), compound 33 was good at defeating myeloid leukaemia (HL-60), lung carcinoma (A549) and myeloid liver carcinoma (SMMC-7721), compound 44 was more selective against myeloid liver carcinoma (SMMC-7721)and lung carcinoma (A549).In summary,41 novel hybrid compounds of benzofuran-imidazolium salts and 8 precursor compounds was designed and synthesis. These compounds showed a good cytotoxic activity and a high degree of selectivity. In the follow-up study, we plan to carry out further structure modification and discuss about its structure-function relationship, mechanism of drug action, etc.And we expect to find lead compounds worthy of further research.